Pyrazole derivatives as herbicides

ABSTRACT

Compounds of the following formula I                    
     wherein                    
     wherein all variables are as defined in the specification and the pyrazoleN-oxides, agrochemically acceptable salts and stereisomers thereof useful as herbisdes.

This application is a 371 of PCT/EP98/01611 filed Mar. 19, 1998.

The present invention relates to novel, herbicidally active substituted pyridone derivatives, to a process for the preparation thereof, to compositions comprising those compounds, and to the use thereof in the control of weeds, especially in crops of useful plants, for example, cereals, maize, rice, cotton, soybean, rape, sorghum, sugar cane, sugar beet, sunflowers, vegetables, plantation crops and fodder plants, or in the inhibition of plant growth. Phenyl-pyrazole compounds having herbicidal activity are known and are described, for example, in EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92,02509, WO 92,06962, WO 95/33728, WO 96/01254 and WO 97/00246.

Surprisingly, it has now been found that substituted pyridono-pyrazole derivatives have excellent herbicidal and growth-inhibiting properties.

The present invention accordingly relates to compounds of formula I

wherein

R₁ is hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl, cyano-C₁-C₄alkyl, C₃- or C₄-alkenyl, C₃- or C₄-haloalkenyl, C₃- or C₄-alkynyl or C₃-C₆cycloalkyl;

R₂ is hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₃-C₆alkenyl, C₃-C₆haloalkenyl, C₃-C₆alkynyl, C₁-C₄alkyl-S(O)₂— or C₁-C₄haloalkyl-S(O)₂—;

R₃ is hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, halogen, cyano, NH₂C(S)—, nitro or amino;

n₁ is 0, 1 or 2;

R₄ is hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₃-C₆alkenyl, C₃-C₆haloalkenyl, C₃-C₆alkynyl or C₃-C₆cycloalkyl;

R₅ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, cyano, nitro, amino, NH₂C(O)—, NH₂C(S)—, C₁-C₄alkylcarbonyl, C₁-C₆alkoxycarbonyl, C₁-C₄haloalkylcarbonyl, C₂-C₄alkenylcarbonyl, C₁-C₃alkyl-CH(OH)—, OHC—, HOC(O)—, ClC(O)—, HON═CH—, C₁-C₄alkoxy-N═CH—, C₂-C₄haloalkenylcarbonyl or C₂-C₄alkynylcarbonyl;

R₁₁ is hydrogen, fluorine, chlorine, bromine or methyl;

R₁₂ is hydrogen, halogen, methyl, halomethyl, nitro, amino, hydroxy, OHC—, HOC(O)—, cyano, C₁-C₄alkoxycarbonyl or halomethoxy;

X₁ is O, S, R₂₀N═ or R₂₅ON═;

R₁₃ is hydroxy, C₁-C₆alkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy, C₃-C₆-haloalkenyloxy, C₁-C₆alkoxy-C₁-C₆alkyl, C₃-C₆alkenyloxy-C₁-C₆alkyl, C₃-C₆alkynyloxy-C₁-C₆alkyl, C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkyl, B₁—C₁-C₆alkoxy, R₂₁(R₂₂)N—, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₂-C₆haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₃-C₆halocycloalkyl, B₁—C₁-C₆alkyl, OHC—, C₁-C₆alkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆haloalkylcarbonyl, C₂-C₆alkenylcarbonyl, C₁-C₆alkoxycarbonyl, C₁-C₆alkyl-S(O)₂—, C₁-C₆haloalkyl-S(O)₂—, (C₁-C₆alkyl)₂N—N═CH—,

B₁—CH═N—, (CH₃)₂N—CH═N—, (C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₅haloalkyl)—CH₂—, (hydroxy-C₁-C₅alkyl)—O— or (B₁—C₁-C₅hydroxyalkyl)—O—;

B₁ is cyano, OHC—, HOC(O)—, C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl, C₃-C₆alkynyloxycarbonyl, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, benzylthio-C(O)—, benzylthio-C(O)— mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, C₁-C₆haloalkoxycarbonyl, C₁-C₆alkylthio-C(O)—, R₂₆(R₂₇)NC(O)—, phenyl, phenyl mono- to tri-substituted by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, C₁-C₆-alkyl-S(O)₂—, C₁-C₆alkyl-S(O)—, C₁-C₆alkylthio, C₃-C₆cycloalkyl, C₁-C₆alkoxy, C₃-C₆alkenylthio or C₃-C₆alkynylthio;

R₂₀ is hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₂-C₆haloalkyl, cyano, R₂₃(R₂₄)N—, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl, C₃-C₆alkynyloxycarbonyl, C₂-C₆haloalkoxycarbonyl, OHC—, C₁-C₆alkylcarbonyl, C₁-C₆haloalkylcarbonyl, C₁-C₆alkyl-S(O)₂—, C₁-C₆haloalkyl-S(O)₂—, phenyl, phenyl mono- to tri-substituted by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, phenyl-C₁-C₆alkyl, or phenyl-C₁-C₆alkyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl;

R₂₁ and R₂₂ are each independently hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆-haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₁-C₆alkoxy-C₁-C₆alkyl, OHC—, C₁-C₆alkylcarbonyl, C₁-C₆haloalkylcarbonyl, C₁-C₆alkyl-S(O)₂— or C₁-C₆haloalkyl-S(O)₂—;

R₂₃ and R₂₄ are each independently as defined for R₂₁;

R₂₅ is hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆haloalkyl, C₃-C₆haloalkenyl, C₁-C₆alkoxy-C₁-C₆alkyl, benzyl, C₁-C₆alkyl-S(O)₂— or C₁-C₆haloalkyl-S(O)₂—;

R₂₆ and R₂₇ are each independently hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆haloalkyl, C₃-C₆haloalkenyl, phenyl, phenyl mono- to tri-substituted by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, benzyl, or benzyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl; or

X₁ and R₁₃ together form a group ═N—Y— wherein Y is bonded to the ring nitrogen atom;

Y is —C(R₃₁)(R₃₂)—CH₂—, —C(R₃₁)(R₃₂)—O—, —C(R₃₁)(R₃₂)—CH₂—CH₂—, —C(R₃₁)(R₃₂)—CH₂—O—, —O—CH₂—, —O—CH₂—CH₂—, —O—CH═CH—, —N(R₃₃)—CH₂—, —N(R₃₃)—CH₂—CH₂—, —N(R₃₃)—CH═CH—, —N(R₃₃)—C(X₃)—CH₂—, —C(X₃)—CH₂—, —C(X₃)—CH₂—CH₂—, —C(X₃)—CH₂—O—, —C(X₃)—O—, —C(R₃₄)═CH—, —C(R₃₁)(R₃₂)—CH═CH—, —C(R₃₄) N—, —C(R₃₁)(R₃₂)—CH═N—, —C(R₃₁)(R₃₂)—N═CH—, —C(X₃)—CH═CH—, —N═N—, —C(R₃₁)(R₃₂)—C(O)—, —C(R₃₁) (R₃₂)—C(S)—, —C(R₃₁)(R₃₂)—CH₂—C(O)—, —C(R₃₁)(R₃₂)—CH₂—C(S)—, —N (R₃₃)—C(O)—, —N (R₃₃)—C(S)—, —N(R₃₃)—CH₂—C(O)—, —N(R₃₃)—CH₂—C(S)—, —O—C(O)—, —O—C(S)—, —C(R₃₄)═CH—C(O)— or —C(R₃₄)═CH—C(S)—, the right-hand end of the bridge members in the above definitions of Y being bonded to the ring nitrogen atom;

R₃₁ is hydrogen, C₁-C₆alkyl or C₁-C₆haloalkyl;

R₃₂ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆haloalkyl, C₂-C₆haloalkenyl, cyano-C₁-C₆alkyl, hydroxy-C₁-C₆alkyl, C₁-C₆alkoxy-C₁-C₆alkyl, C₃-C₆alkenyloxy-C₁-C₆alkyl, C₃-C₆alkynyloxy-C₁-C₆alkyl, C₁-C₆alkylcarbonyloxy-C₁-C₆alkyl, C₁-C₆haloalkylcarbonyloxy-C₁-C₆alkyl, carboxyl, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl, C₃-C₆alkynyloxycarbonyl, C₁-C₆haloalkoxycarbonyl, C₃-C₆cycloalkoxycarbonyl, C₁-C₄alkoxy-C₁-C₆alkoxycarbonyl, C₁-C₆alkyl-NHC(O)—, (C₁-C₆alkyl)₂NC(O)—, C₃-C₆alkenyl-NHC(O)—, C₁-C₆alkyl-(C₃-C₆-alkenyl)NC(O)—, C₃-C₆alkynyl-NHC(O)—, aminocarbonyl, C₁-C₆alkylthio-C(O)—, C₃-C₆-alkenylthio-C(O)—, C₃-C₆alkynylthio-C(O)—, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, phenoxycarbonyl, C₁-C₆alkyl-S(O)₂NHC(O)—, C₁-C₆alkyl-S(O)₂(C₃-C₆alkenyl)N—C(O)—, C₁-C₆haloalkyl-S(O)₂NHC(O)—, HON═CH—, C₁-C₆alkoxy-N═CH—, C₃-C₆alkenyloxy-N═CH—, C₃-C₆alkynyloxy-N═CH—, HOC(O)—C₁-C₆alkyl, C₁-C₆alkoxycarbonyl-C₁-C₆alkyl, C₃-C₆alkenyloxycarbonyl-C₁-C₆alkyl, C₃-C₆alkynyloxycarbonyl-C₁-C₆alkyl, C₁-C₆alkylcarbonyl, ClC(O)—, H₂NC(S)—, OHC—, cyano, phenyl, phenyl mono- to tri-substituted by halogen, C₁-C₄alkyl or by C₁-C₄-haloalkyl, phenyl-C₁-C₆alkyl, or phenyl-C₁-C₆alkyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl;

X₃ is O, S, R₂₀N═ or R₂₅ON═;

R₃₃ is hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₁-C₆alkylcarbonyl, C₁-C₆haloalkylcarbonyl, C₁-C₆alkyl-S(O)₂— or B₂—C₁-C₆-alkyl;

B₂ is cyano, HOC(O)—, C₁-C₆alkoxycarbonyl, C₁-C₆alkylcarbonyl or C₁-C₆alkoxy; and

R₃₄ is as defined for R₃₂ or is halogen, C₁-C₆alkoxy, C₃-C₆alkenyloxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkyl-S(O)— or C₁-C₆alkyl-S(O)₂—,

and also to the pyrazole N-oxides, agrochemically acceptable salts and stereoisomers of those compounds of formula I.

In the above definitions, halogen is to be understood as meaning iodine or, preferably, fluorine, chlorine or bromine.

The alkyl, alkenyl and alkynyl groups in the substituent definitions may be straight-chain or branched, this applying also to the alkyl, alkenyl and alkynyl moiety of the alkylcarbonyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, alkylthio, alkylthio-C(O)—, alkylsulfonyl, alkylaminocarbonyl, dialkylaminocarbonyl, B₁-alkyl and HOC(O)-alkyl groups. Alkyl groups are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl and the various isomers of pentyl and hexyl. Methyl, ethyl, n-propyl, isopropyl and n-butyl are preferred.

There may be mentioned as examples of alkenyl radicals vinyl, allyl, methallyl, 1-methylvinyl, but-2-en-1-yl, pentenyl and 2-hexenyl, with preference being given to alkenyl radicals having a chain length of from 3 to S carbon atoms.

There may be mentioned as examples of alkynyl radicals ethynyl, propargyl, 1-methylpropargyl, 3-butynyl, but-2-yn-1-yl, 2-methylbutyn-2-yl, but-3-yn-2-yl, 1-pentynyl, pent-4-yn-1-yl and 2-hexynyl, with preference being given to alkynyl radicals having a chain length of from 2 to 4 carbon atoms.

Suitable haloalkyl radicals are alkyl groups that are mono- or poly-substituted, especially mono- to tri-substituted, by halogen, halogen being in particular iodine or especially fluorine, chlorine or bromine, for example fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2-chloroethyl, 2,2-dichloroethyl, 2,2,2-trifluoroethyl and 2,2,2-trichloroethyl.

Suitable haloalkenyl radicals are alkenyl groups mono- or poly-substituted by halogen, halogen being in particular bromine, iodine or especially fluorine or chlorine, for example 2- or 3-fluoropropenyl, 2- or 3-chloropropenyl, 2- or 3-bromopropenyl, 2,3,3-trifluoropropenyl, 2,3,3-trichloropropenyl, 4,4,4-trifluorobut-2-en-1-yl and 4,4,4-trichlorobut-2-en-1-yl. Of the alkenyl radicals mono-, di- or tri-substituted by halogen, preference is given to those having a chain length of 3 or 4 carbon atoms. The alkenyl groups may be substituted by halogen at saturated or unsaturated carbon atoms.

Alkylsulfonyl is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropyisulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl or an isomer of pentylsulfonyl or hexylsulfonyl; preferably methylsulfonyl or ethylsulfonyl.

Haloalkylsulfonyl is, for example, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, chloromethylsulfonyl, trichloromethylsulfonyl, 2-fluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl or 2,2,2-trichloroethylsulfonyl.

Alkenylsulfonyl is, for example, allyisulfonyl, methallylsulfonyl, but-2-en-1-ylsulfonyl, pentenylsulfonyl or 2-hexenylsulfonyl.

Haloalkenylsulfonyl is, for example, 2- or 3-fluoropropenylsulfonyl, 2- or 3-chloropropenylsulfonyl, 2- or 3-bromopropenylsulfonyl, 2,3,3-trifluoropropenylsulfonyl, 2,3,3-trichloropropenylsulfonyl, 4,4,4-trifluorobut-2-en-1-ylsulfonyl or 4,4,4-trichlorobut-2-en-1-ylsulfonyl.

Cyanoalkyl is, for example, cyanomethyl, cyanoethyl, cyanoeth-1-yl or cyanopropyl. Hydroxyalkyl is, for example, hydroxymethyl, 2-hydroxyethyl or 3-hydroxypropyl.

Alkylamino is, for example, methylamino, ethylamino or an isomer of propyl- or butyl-amino.

Dialkylamino is, for example, dimethylamino, diethylamino or an isomer of dipropyl- or dibutyl-amino.

Alkenylamino is, for example, allylamino, methallylamino or but-2-en-1-ylamino.

Alkynylamino is, for example, propargylamino or 1-methyipropargylamino.

Haloalkylamino is, for example, chloroethylamino, trifluoroethylamino or 3-chloropropylamino.

Di(haloalkyl)amino is, for example, di(2-chloroethyl)amino.

Alkylcarbonyl is especially acetyl or propionyl.

Haloalkylcarbonyl is especially trifluoroacetyl, trichloroacetyl, 3,3,3-trifluoropropionyl or 3,3,3-trichloropropionyl.

Alkenylcarbonyl is especially vinylcarbonyl, allylcarbonyl, methallylcarbonyl, but-2-en-1-yl-carbonyl, pentenylcarbonyl or 2-hexenylcarbonyl.

Alkynylcarbonyl is especially acetylenecarbonyl, propargylcarbonyl, 1-methylpropargylcarbonyl, 3-butynylcarbonyl, but-2-yn-1-ylcarbonyl or pent-4-yn-1-ylcarbonyl.

Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy or an isomer of pentyloxy or hexyloxy.

Alkenyloxy is, for example, allyloxy, methallyloxy or but-2-en-1-yloxy.

Alkynyloxy is, for example, propargyloxy or 1-methylpropargyloxy.

Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxymethyl or isopropoxyethyl.

Alkenyloxyalkyl is, for example, allyloxyalkyl, methallyloxyalkyl or but-2-en-1-yloxyalkyl.

Alkynyloxyalkyl is, for example, propargyloxyalkyl or 1-methylpropargyioxyalkyl.

Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, iso-propoxycarbonyl or n-butoxycarbonyl, preferably methoxycarbonyl or ethoxycarbonyl.

Alkenyloxycarbonyl is, for example, allyloxycarbonyl, methallyloxycarbonyl, but-2-en-1-yl-oxycarbonyl, pentenyloxycarbonyl or 2-hexenyloxycarbonyl.

Alkynyloxycarbonyl is, for example, propargyloxycarbonyl, 3-butynyloxycarbonyl, but-2-yn-1-yloxycarbonyl or 2-methylbutyn-2-yloxycarbonyl.

Alkoxyalkoxycarbonyl is, for example, methoxymethoxycarbonyl, ethoxymethoxycarbonyl, ethoxyethoxycarbonyl, propoxymethoxycarbonyl, propoxyethoxycarbonyl, propoxypropoxycarbonyl or butoxyethoxycarbonyl.

Haloalkoxy is, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy or 2,2,2-trichloroethoxy.

Of the alkenyl radicals mono-, di- or tri-substituted by halogen, preference is given to those having a chain length of 3 or 4 carbon atoms. The alkenyloxy groups may be substituted by halogen at saturated or unsaturated carbon atoms.

Suitable haloalkenyloxy radicals are alkenyloxy groups mono- or poly-substituted by halogen, halogen being in particular bromine, iodine or especially fluorine or chlorine, for example 2- or 3-fluoropropenyloxy, 2- or 3-chloropropenyloxy, 2- or 3-bromopropenyloxy, 2,3,3-trifluoropropenyloxy, 2,3,3-trichloropropenyloxy, 4,4,4-trifluoro-but-2-en-1-yloxy and 4,4,4-trichlorobut-2-en-1-yloxy.

The cycloalkyl radicals suitable as substituents are, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

The cycloalkoxycarbonyl radicals suitable as substituents are, for example, cyclopropoxycarbonyl, cyclobutoxycarbonyl, cyclopentyloxycarbonyl and cyclohexyloxycarbonyl.

The halocycloalkyl radicals suitable as substituents are, for example, mono-, di- or up to perhalogenated cycloalkyl radicals, for example, fluorocyclopropyl, chlorocyclopropyl, bromocyclopropyl, 2,2-dichlorocyclopropyl, 2,2-difluorocyclopropyl, 2,2-dibromocyclopropyl, 2-fluoro-2-chlorocyclopropyl, 2-chloro-2-bromocyclopropyl, 2,2,3,3-tetrafluorocyclopropyl, 2,2,3,3-tetrachlorocyclopropyl, pentafluorocyclopropyl, fluorocyclobutyl, chlorocyclobutyl, 2,2-difluorocyclobutyl, 2,2,3,3-tetrafluorocyclobutyl, 2,2,3-trifluoro-3-chlorocyclobutyl, 2,2-dichloro-3,3-difluorocyclobutyl, fluorocyclopentyl, difluorocyclopentyl, chlorocyclopentyl, perfluorocyclopentyl, chlorocyclohexyl and pentachlorocyclohexyl.

Alkylthio is, for example, methylthio, ethylthio, propylthio or butylthio or a branched isomer thereof.

Phenyl or benzyl per se, or as part of a substituent, such as, for example, phenoxycarbonyl or benzyloxycarbonyl, may be unsubstituted or substituted, in which case the substituents may be in the ortho-, meta- or para-position. Substituents are, for example, C₁-C₄alkyl, C₁-C₄alkoxy, halogen or C₁-C₄haloalkyl.

Corresponding meanings may also be given to the substituents in combined definitions, such as, for example, in alkyl-S(O)—, alkoxy-N═CH—, (alkyl)₂N-C(O)—, (alkyl)₂N—N═CH—, alkenyl-NHC(O)—, alkyl(alkenyl)N—C(O)—, alkynyl-NHC(O)—, alkylcarbonyloxyalkyl, alkoxycarbonylalkyl, haloalkoxycarbonyl, haloalkylcarbonyloxyalkyl, haloalkenylcarbonyl, alkyl-S(O)₂—NHC(O)—, haloalkyl-S(O)₂NHC(O)—, B₁-alkoxy and B₂-alkyl.

In the definition of R₁₃, (C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₅hydroxyalkyl)—CH₂— and (B₁—C₁-C₆-haloalkyl)—CH₂— signify that only the C₁-C₅alkyl moiety is hydroxylated or halogenated, that is to say, the methylene group is not hydroxylated or halogenated.

In the definition of X₁ and R₁₃ together, a group ═N—Y— wherein Y is bonded to the ring nitrogen atom is to be understood as meaning one of the following bicyclic ring systems of formula I:

In the definition of Y, it is always the right-hand end of the bridge member that is bonded to the ring nitrogen atom, as is illustrated, for example where Y is —C(R₃₁)(R₃₂)—CH₂—, —C(R₃₁)(R₃₂)—O— and —C(R₃₄)═CH—, in the following bicyclic ring structures:

In the definitions of cyanoalkyl, alkylcarbonyl, alkenylcarbonyl, haloalkenylcarbonyl, alkynylcarbonyl, alkoxycarbonyl, alkylthiocarbonyl and haloalkylcarbonyl, the upper and lower limits of the number of carbon atoms given in each case do not include the cyano or carbonyl carbon atom, as the case may be.

The compounds of formula I may, in respect of the group W (W1 to W3), be present in the form of mixtures consisting of the isomers substituted in the 3- and 5-positions of the pyrazole ring by the pyridone group (pyridone), for example in the form of regioisomers IW1a and IW1b

for the group W1. The ratio of isomers may vary as a function of the method of synthesis.

The invention relates also to the salts that the compounds of formula I having azide hydrogen, especially the derivatives having carboxylic acid groups and sulfonamide groups (for example carboxy-substituted alkyl, alkoxy and pyridone groups (R₁₂) and alkyl-S(O)₂NH— and haloalkyl-S(O)₂NH— groups), are capable of forming with bases. Those salts are, for example, alkali metal salts, for example sodium and potassium salts; alkaline earth metal salts, for example calcium and magnesium salts; ammonium salts, that is to say unsubstituted ammonium salts and mono- or poly-substituted ammonium salts, for example triethylammonium and methylammonium salts; or salts with other organic bases.

Of the alkali metal and alkaline earth metal hydroxides as salt farmers, attention is drawn, for example, to the hydroxides of lithium, sodium, potassium, magnesium and calcium, but especially to the hydroxides of sodium and potassium.

Examples of amines suitable for ammonium salt formation include ammonia as well as primary, secondary and tertiary C₁-C₁₈alkylamines, C₁-C₄hydroxyalkylamines and C₂-C₄-alkoxyalkylamines, for example methylamine, ethylamine, n-propylamine, isopropylamine, the four isomers of butylamine, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine, ethylheptylamine, ethyloctylamine, hexylheptylamine, hexyloctylamine, dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-butylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, ethanolamine, n-propanolamine, isopropanolamine, N,N-diethanolamine, N-ethylpropanolamine, N-butylethanolamine, allylamine, n-butenyl-2-amine, n-pentenyl-2-amine, 2,3-dimethylbutenyl-2-amine, dibutenyl-2-amine, n-hexenyl-2-amine, propylenediamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, tri-sec-butylamine, tri-n-amylamine, methoxyethylamine and ethoxyethylamine; heterocyclic amines, for example pyridine, quinoline, isoquinoline, morpholine, thiomorpholine, piperidine, pyrrolidine, indoline, quinuclidine and azepine; primary arylamines, for example anilines, methoxyanilines, ethoxyanilines, o-, m- and p-toluidines, phenylenediamines, benzidines, naphthylamines and o-, m- and p-chloroanilines; especially triethylamine, isopropylamine and diisopropylamine.

The salts of compounds of formula I having basic groups, especially having basic pyrazolyl rings, or of derivatives having amino groups, for example alkylamino and dialkylamino groups, in the definition of R₃, R₅ or R₁₃ are, for example, salts with inorganic or organic acids, for example hydrohalic acids, such as hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydriodic acid, and also sulfuric acid, phosphoric acid, nitric acid, and organic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycolic acid, thiocyanic acid, citric acid, benzoic acid, oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid.

The possible presence of at least one asymmetrical carbon atom in the compounds of formula I, for example in the substituent R₁₃, where R₁₃ is a branched alkyl, alkenyl, haloalkyl or alkoxyalkyl group or where R₁₃ is (B₁—C₁-C₆hydroxyalkyl)—CH₂— wherein, for example, B₁ is C₁-C₆alkyl-S(O)—, means that the compounds may occur in the form of optically active single isomers or in the form of racemic mixtures. In the present invention, “compounds of formula I” is to be understood as including both the pure optical antipodes and the racemates or diastereoisomers. When an aliphatic C═C or C═N—O double bond (syn/anti) is present, geometric isomerism may occur. The invention relates to those isomers also.

Preferred compounds of formula I correspond to formula 1a

wherein

R₁, R₂, R₃, R₄, R₅, R₁₁, R₁₂, R₁₃, X₁ and n₁ are as defined for formula I. Of the compounds of formula Ia, preference is given to those wherein in the group Wa R₃ is C₁-C₄alkyl or halogen; and R₁ is methyl or ethyl.

Special preference is given to compounds of formula Ia wherein R₃ is methyl, halomethyl, chlorine or bromine. Of those, the compounds wherein Wa is a group W1a or W2a are especially important.

Also especially important are compounds of formula 1a wherein Wa is the group W3a; and R₅ is C₁- or C₂-halomethyl, cyano or H₂NC(S)—.

Also particularly important are compounds of formula 1a wherein Wa is the group W1a; R₁ is C₁-C₆alkyl; R₂ is C₁- or C₂-haloalkyl; R₃ is chlorine, bromine, methyl or halomethyl; R₁ is fluorine, chlorine or bromine; and R₁₂ is halogen, methyl or halomethyl. Of those, compounds in which R₁ is methyl or ethyl; and R₂ is difluoromethyl are more especially important.

Special preference is given also to compounds of formula 1a wherein Wa is the group W2a; R₁ is C₁-C₄alkyl; R₄ is methyl or ethyl; R₃ is chlorine, bromine or methyl; R₁, is fluorine, chlorine or bromine; and R₁₂ is halogen, methyl or halomethyl. Of those compounds, those wherein R₁ is methyl or ethyl; and R₄ is methyl are more especially preferred. Particularly important compounds of formula 1a are those wherein Wa is the group W3a; R₁ is C₁-C₄alkyl; R₅ is C₁- or C₂-haloalkyl, cyano, H₂NC(S)— or CH₃C(O)—; R₃ is chlorine, bromine, methyl or halomethyl; R₁₁ is fluorine, chlorine or bromine; and R₁₂ is halogen, methyl or halomethyl. Of those, especially compounds wherein R₁ is methyl or ethyl; and R₅ is halomethyl or cyano are more especially important.

The process according to the invention for the preparation of a compound of formula I

wherein R₁₁, R₁₂ and W are as defined for formula I; X₁ is O or S; R₁₃ is C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₂-C₆haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₃-C₆halocycloalkyl, B₁-C₁-C₆alkyl,

(C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₅hydroxyalkyl)—CH₂— or (B₁—C₁-C₅haloalkyl)—CH₂—; and B₁ is as defined for formula I, is carried out analogously to known processes and comprises oxidising a compound of formula III

for example with hydrogen peroxide-urea adduct in the presence of carboxylic acids and/or carboxylic acid anhydrides, organic peracids or persulfonic acid (Caro's acid) in a suitable solvent, to form a compound of formula V

and subsequently rearranging that compound in an inert solvent in the presence of an anhydride or in the presence of antimony pentachloride to yield, after aqueous working up, a compound of formula II

the radicals R₁₁, R₁₂ and W in the compounds of formulae 11, II and V being as defined above, and then alkylating that compound in the presence of an inert solvent and a base with a compound of formula VI

R₁₃—L  (VI),

wherein R₁₃ is as defined above and L is a leaving group, preferably chlorine, bromine, iodine, CH₃SO₂O— or

to form the isomeric compounds of formulae I and IV

wherein R₁₁, R₁₂, R₁₃ and W are as defined above and X₁ is O, and subsequently, where appropriate after separating off the compound of formula I, functionalising the pyridone group thereof according to the definition of X₁ and R₁₃, if desired, for example, converting it with the aid of a suitable sulfur reagent into the corresponding pyridinethione derivative (X₁═S) (Reaction Scheme 1).

The process according to the invention for the preparation of a compound of formula I

wherein R₁₁, R₁₂ and W are as defined for formula I; X₁ is S; R₁₃ is hydroxy, C₁-C₆alkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy, C₃-C₆haloalkenyloxy, B₁—C₁-C₆alkoxy, C₁-C₆alkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆haloalkylcarbonyl, C₂-C₆alkenylcarbonyl or C₁-C₆alkoxycarbonyl; and B₁ is as defined for formula I, is carried out analogously to known processes and comprises first of all oxidising a compound of formula III

to yield a compound of formula V

chlorinating or brominating that compound to form a compound of formula VIII

the radicals R₁₁, R₁₂ and W in the compounds of formulae III, V and VIII being as defined above and Hal in the compound of formula VIII being chlorine or bromine, subsequently converting the compound of formula VIII with a suitable sulfur reagent, for example thiourea, sodium hydrogen sulfide (NaSH) or phosphorus pentasulfide (P₂S₅), in the presence of a solvent into a compound of formula Ic

and reacting that compound in the presence of a solvent and a base with a compound of formula XI

R₁₄—L  (XI),

wherein R₁₄ is C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆haloalkyl, C₃-C₆haloalkenyl, B₁—C₁-C₆alkyl or C₁-C₆alkylcarbonyl; B₁ is as defined above; and L is a leaving group (Reaction Scheme 2).

The process according to the invention for the preparation of a compound of formula I

wherein R₁₁, R₁₂, R₁₃ and W are as defined for formula I and XI is S is carried out analogously to known processes and comprises treating a compound of formula I

wherein R₁₁, R₁₂, R₁₃ and W are as defined above and X₁ is O, with a sulfur reagent in an inert solvent.

The preparation of compounds of formula I wherein X₁ is O or S; and R₁₃ is C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₂-C₆haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₃-C₆halocycloalkyl, B₁—C₁-C₆alkyl,

(C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₅hydroxyalkyl)—CH₂— or (B₁—C₁-C₅haloalkyl)—CH₂—; and B₁ is as defined for formula I is illustrated in the following Reaction Scheme 1.

The pyridine N-oxides of formula V (Reaction Scheme 1) can be prepared according to known methods (e.g. Org. Synth. 4, 828 (1963); ibid. 3, 619 (1955); U.S. Pat. No. 3,047,579; and B. Iddon and H. Suschitzky in “Polychloroaromatic Compounds”, Editor H. Suschitzky, Plenum Press, London 1974, page 197), advantageously by reaction of a pyridine derivative of formula III with an oxidising agent, such as, for example, an organic peracid, for example m-chloroperbenzoic acid (MCPBA), peracetic acid or pertrifluoroacetic acid, or aqueous hydrogen peroxide solution or hydrogen peroxide-urea adduct together with a carboxylic acid and/or a carboxylic acid anhydride, or an inorganic peracid, for example pertungstic acid. Solvents suitable for that reaction are, for example, water, organic acids, for example acetic acid and trifluoroacetic acid, halogenated hydrocarbons, for example dichloromethane and 1,2-dichloroethane, esters, for example ethyl acetate, ethers, for example tetrahydrofuran and dioxane, or mixtures of those solvents. The reaction temperatures are generally in the range from −20° C. to 100° C., depending on the solvent or mixture of solvents used.

The 6-hydroxypyridine derivatives of formula II can be prepared according to known methods (e.g. Quart. Rev. 10, 395 (1956); J. Am. Chem. Soc. 85, 958 (1963); and J. Org. Chem. 26, 428 (1961)), advantageously by rearrangement of the pyridine N-oxides of formula V in the presence of an anhydride, for example acetic anhydride, trifluoroacetic anhydride or methanesulfonic anhydride, in a suitable inert solvent, such as, for example, a halogenated hydrocarbon, for example dichloromethane or 1,2-dichloroethane, an amide, for example N,N-dimethylformamide or 1-methyl-2-pyrrolidone (NMP), and, where appropriate, in the presence of sodium acetate. The reaction temperatures are generally in the range from −30° C. to 80° C.

The 6-O-acyl- or 6-O-sulfonyl-pyridines formed first can readily be hydrolysed, by aqueous working up of the reaction mixture, to form the desired 6-hydroxypyridines of formula II. Analogously to Tetrahedron 37, 187 (1981), as a further variant it is possible to use antimony pentachloride in the above rearrangement reaction.

The subsequent alkylation may be carried out according to known methods (e.g. Org. Prep. Proced. Int. 9, 5 (1977); J. Org. Chem. 35, 2517 (1970); ibid. 32, 4040 (1967); and Tetrahedron Lett. 36, 8917 (1995) as well as Preparation Examples P20 and P21), advantageously using an alkylation reagent of formula VI. The alkylation usually results in an isomeric mixture consisting of the compounds of formulae I (N-alkylation) and IV (O-alkylation).

Suitable solvents are, for example, alcohols, for example methanol, ethanol and isopropanol, amides, for example N,N-dimethylformamide (DMF) and 1-methyl-2-pyrrolidone (NMP), sulfoxides, for example dimethyl sulfoxide (DMSO), and sulfones, for example sulfolan, or mixtures of the above solvents with water, ethers, for example diethyl ether, tert-butyl methyl ether, dimethoxyethane (DME), dioxane and tetrahydrofuran (THF), esters, for example ethyl acetate, ketones, for example acetone and methyl ethyl ketone, and hydrocarbons, for example n-hexane, toluene and xylenes.

Suitable bases are organic and inorganic bases, for example alkali metal alcoholates, for example sodium methanolate, sodium ethanolate and potassium tert-butanolate, trialkylammonium hydroxides, trialkylammonium halides, for example triethylammonium iodide, alkali metal and alkaline earth metal hydrides, for example sodium hydride together with lithium bromide (2 equivalents), alkali metal carbonates, for example potassium carbonate, alkali metal hydroxides, for example sodium and potassium hydroxide, and also caesium fluoride.

The reaction temperatures for the alkylation are in the range from −20° C. to the reflux temperature of the solvent used, preferably from 0° C. to 50° C. The isomers of formulae I and IV can readily be separated by means of silica gel chromatography or fractional crystallisation.

Optionally, the desired pyridone derivative of formula I separated from the secondary product of formula IV can readily be converted into the corresponding pyridinethione derivative (X₁═S) according to known methods (e.g. Bull. Soc. Chim. Fr. 1953, 1001; and J. Am. Chem. Soc. 73, 3681 (1951)), for example with the aid of a suitable sulfur reagent, for example Lawesson's reagent or phosphorus pentasulfide in an inert solvent, such as, for example, a xylene, pyridine or sulfolan. The reaction temperatures are generally in the range from 20° C. to the boiling temperature of the solvent used.

The preparation of compounds of formula I wherein X₁ is S; and R₁₃ is hydroxy, C₁-C₆alkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy, C₃-C₆haloalkenyloxy, B₁—C₁-C₆alkoxy, C₁-C₆alkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆haloalkylcarbonyl, C₂-C₆alkenylcarbonyl or C₁-C₆alkoxycarbonyl; and B₁ is as defined for formula I is illustrated in the following Reaction Scheme 2.

The procedure for the preparation of pyridine N-oxides of formula V (Reaction Scheme 2) is analogous to that indicated under Reaction Scheme 1.

The pyridine N-oxides of formula V can be converted into the corresponding 6-chloro- or 6-bromo-pyridine derivatives of formula VIII analogously to known processes (e.g. Heterocycles 30, 875 (1990); Can. J. Chem. 31, 457 (1953); and J. Org. Chem. 19, 1633 (1954)), advantageously using a halogenating agent, for example phosphorus oxychloride, phosphorus oxybromide, sulfuryl chloride, thionyl chloride or phosphorus pentachloride in phosphorus oxychloride. The halogenation can generally be carried out at temperatures of from 20° C. to 100° C.

The reaction of the halopyridine N-oxides of formula VII to form the compound of formula Ic can be effected analogously to known processes (e.g. U.S. Pat. No. 2,742,476, U.S. Pat. No. 2,809,971, J. Am. Chem. Soc. 72, 4362 (1950) and J. Chem. Soc. 1939, 1858), advantageously using a suitable sulfur reagent, such as, for example, hydrogen sulfide, sodium hydrogen sulfide or thiourea, in a solvent, such as, for example, water, an alcohol, for example ethanol, or a water/alcohol mixture, or an amide, for example N,N-dimethylformamide (DMF) or NMP. The reaction is generally carried out at temperatures of from −10° C. to 100° C.

The reaction of the compound of formula Ic with the reactive reagent of formula XI, wherein L is a leaving group, such as, for example, halogen, for example chlorine, bromine or iodine,

or, in the case where R₁₄ is C₁-C₆alkylcarbonyl and there is used as reactive reagent of formula XI the corresponding acid anhydride, C₁-C₆alkylcarbonyloxy, can be carried out analogously to known processes (e.g. Tetrahedron Lett. 31, 1965 (1990); Tetrahedron 1991, 7091; and J. Org. Chem. 54, 4330 (1989)). Advantageously, equimolar amounts of compound of formula Ic and reactive reagent of formula XI are reacted at temperatures of from 0° C. to 100° C. in the presence of a solvent and a base.

Suitable solvents include the familiar inert organic solvents, such as, for example, chlorinated hydrocarbons, for example dichloromethane, aromatic hydrocarbons, for example benzene, toluene and pyridine, ethers, for example dioxane and DME, amides, for example N,N-dimethylformamide and NMP, and sulfoxides, for example DMSO. Suitable bases include the known inorganic and organic bases, such as, for example, alkali metal and trialkylammonium hydroxides, for example sodium or potassium hydroxide and triethylammonium hydroxide, respectively, carbonates, for example sodium and potassium carbonate, and alcoholates, for example sodium ethanolate or potassium isopropanolate. The reaction may also, where appropriate, be carried out under phase transfer conditions. There may be used as phase transfer catalysts the customary quaternary ammonium salts, such as, for example tetraoctylammonium bromide and benzyltriethylammonium chloride. Under those conditions, a suitable organic solvent is any inert non-polar solvent, such as, for example, benzene or toluene.

The preparation of compounds of formula I wherein X₁ is S; and R₁₃ is C₁-C₆alkoxy-C₁-C₆-alkyl, C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₂-C₆haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₃-C₆halocycloalkyl, B₁—C₁-C₆alkyl,

(C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₅hydroxyalkyl)—CH₂— or (B₁—C₁-C₆haloalkyl)—CH₂—; and B₁ is as defined for formula I is illustrated in the following Reaction Scheme 3.

The conversion of the pyridone derivatives of formula I wherein R₁₁, R₁₂, R₁₃ and W are as defined for formula I and X₁ is O into the corresponding pyridinethione derivatives of formula I wherein X₁ is S (Reaction Scheme 3) can be carried out analogously to known processes (e.g. J. Het. Chem. 25, 511 (1988); ibid. 22, 265 (1985); Bull. Soc. Chim. Fr. 1953, 1001; J. Prakt. Chem. 1988, 293; Chem. Ber. 62, 2732 (1929); Chem. Heterocycl. Compd. (Engl. Transl.) 1988, 658; Pharmazie 45, 731 (1990); and J. Prakt. Chem./Chem-Ztg 334, 119 (1992)), advantageously with the aid of a sulfur reagent, such as, for example, P₂S₅ or Lawesson's reagent, in an organic solvent, such as, for example, an aromatic hydrocarbon, for example benzene, toluene, a xylene or pyridine, a halogenated aromatic hydrocarbon, for example dichlorobenzene, or an amide, for example DMF or NMP. The reaction temperatures are generally in the range from 20° C. to 200° C. depending on the solvent used.

The compounds lying within the scope of formula I wherein X₁ and R₁₃ together form a group ═N—Y— and Y is, for example, a bridge member —C(R₃₁)(R₃₂)—CH₂— can be prepared analogously to known processes, as described, for example, in Sov, Prog. Chem. (Engl. Transl.) 42, 65 (1976); J. Chem. Soc., Perkin Trans 1 1976, 201; Justus Liebigs Ann. 1978, 1491; and Helv. Chim. Acta 73, 1679 (1990).

The compounds lying within the scope of formula I wherein X₁ and R₁₃ together form a group ═N—Y— and Y is, for example, a bridge member —C(R₃₄)═CH— can be prepared analogously to known processes, as described, for example, in Farmaco Ed. Sci. 37, 22 (1982); J. Chem. Res. (Miniprint) II, 3368 (1986); and J. Chem. Soc., Perkin Trans 1 1987, 1159.

Taking into consideration the chemical properties of the pyridyl or pyridonyl moiety, as the case may be, all other compounds within the scope of formula I can readily be prepared, in terms of the construction of the pyrazole rings, in a manner analogous to that described in Preparation Examples P1 to P21, or as described, for example, in “Methoden der Organ-ischen Chemie” (Houben-Weyl), Volume E 8b, Georg Thieme Verlag Stuttgart, 1994, page 399 ff.; or in “Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings”, Editor R. H. Wiley, Interscience Publishers, John Wiley & Sons, New York, 1967, page 1 ff.; or as described in the patent specifications WO 96/01254 and WO 97/00246.

A large number of known standard processes are available for the preparation of the pyridine derivatives of formula III, the choice of a suitable process being governed by the properties (reactivities) of the substituents in the respective intermediates. A number of specimen examples are also given in Preparation Examples P1 to P16. For example, a compound of formula III

wherein W is a group

R₁, R₂, R₁₁ and R₁₂ are as defined for formula I; and R₃ is hydrogen, halogen, C₁-C₄alkyl or C₁-C₄haloalkyl, can be prepared starting from, for example, a compound of formula XII

wherein R₁₁ and R₁₂ are as defined above, which is reacted in an alcohol of formula XIII

R₈—OH  (XIII),

wherein R₈ is C₁-C₄alkyl, in the presence of a suitable palladium or nickel catalyst, such as, for example, palladium bis(triphenylphosphine) dichloride (PdCl₂(PPh₃)₂) and a base, such as, for example, triethylamine, under carbon monoxide excess pressure, to form a compound of formula XIV

wherein R₈, R₁₁ and R₁₂ are as defined above, which is subjected to acid or basic hydrolysis to form the corresponding carboxylic acid of formula XV

and converted with a carboxylic acid halogenating reagent, such as, for example, thionyl chloride, phosphorus pentachloride or oxalyl chloride, into the corresponding carboxylic acid halide of formula XVI

wherein R₁₁ and R₁₂ are as defined above and X₂ is halogen, preferably chlorine, and that compound is reacted in a solvent, such as, for example, acetonitrile in the presence of an alkaline earth metal salt, preferably magnesium chloride, and a base, such as, for example, triethylamine, with the malonic acid mono ester salt of formula XVII

wherein R₃ is hydrogen, C₁-C₄alkyl or C₁-C₄haloalkyl; M₁ ⁺ is an alkali metal ion, preferably a potassium ion; and R₇ is C₁-C₄alkoxy, to yield the keto ester of formula XIX

wherein R₃, R₇, R₁₁ and R₁₂ are as defined above, and that compound is cyclised in a solvent, such as, for example, glacial acetic acid, with a compound of formula XX

NH₂NH—R₁  (XX),

wherein R₁ is as defined for formula I, to yield a compound of formula XXI

wherein R₁, R₃, R₁₁ and R₁₂ are as defined above, and subsequently in accordance with standard methods the hydroxyl group is functionalised, especially freonised (Example P13), according to the definition of R₂, and the pyrazole ring is optionally halogenated (R₃ is halogen; Example P14) or oxidised to the corresponding pyridine N-oxide (Example P17). The compounds of formula XXII

wherein R₁, R₃, R₅, R₁₁ and R₁₂ are as defined for formula I, are important intermediates for the preparation of compounds of formula III, especially compounds of formula III wherein W is a group W3; R₅ is haloalkyl (Example P11); and R₁, R₃, R₁₁ and R₁₂ are as defined for formula I.

The compounds of formula XXII are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.

The compounds of formula XIX

wherein R₁₁ and R₁₂ are as defined for formula I; R₃ is hydrogen, C₁-C₄alkyl or C₁-C₄-haloalkyl; and R₇ is C₁-C₄alkoxy, C₁- or C₂₋haloalkyl or C₁-C₄alkoxycarbonyl, are important intermediates for the preparation of compounds of formula I, especially compounds of formula I wherein W is a group

R₁, R₂, R₁₁ and R₁₂ are as defined for formula I; and R₃ is hydrogen, halogen, C₁-C₄alkyl or C₁-C₄haloalkyl. The compounds of formula XXIII

wherein R₁₁ and R₁₂ are as defined for formula I; and R₃ is hydrogen, halogen, C₁-C₄alkyl or C₁-C₄haloalkyl, are important intermediates for the preparation of compounds of formula 1a wherein Wa is a group W3a; R₅ is hydrogen; and R₁, R₃, R₁, and R₁₂ are as defined for formula I (Example 8).

The compounds of formula XXIII are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.

The compounds of formula XXIV

wherein R₁₁ and R₁₂ are as defined for formula I; and R₃ is hydrogen, C₁-C₄alkyl or C₁-C₄-haloalkyl, are important intermediates for the preparation of compounds of formula I wherein W is a group

R₃ is hydrogen, C₁-C₄alkyl or C₁-C₄haloalkyl; R₅ is amino; and R₁, R₁₁ and R₁₂ are as defined for formula I.

The compounds of formula XXIV are prepared according to EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.

A large number of known standard processes are available for the preparation of the pyridonylpyrazoles of formula I substituted at the pyridone ring, the choice of a suitable preparation process being governed by the properties (reactivities) of the substituents in the respective intermediates.

A number of specimen examples are also given in Preparation Examples P19 to P24. The compound of formula XII, and the starting compounds 2,5-dichloro-3-fluoropyridine, 2,3-dichloro-5-trifluoromethylpyridine and 3,5-dichloro-2-acetylpyridine used in Preparation Examples P1, P2 and P9, are either known or can be prepared analogously to published processes.

The reagents of formulae VI and XI used in the Reaction Schemes 1, 2 and 3 are either known or can be prepared analogously to published processes.

All other compounds within the scope of formula I can readily be prepared, taking into consideration the respective chemical reactivities, analogously to the processes according to Preparation Examples P1 to P25, or analogously to the methods described in “Methoden der Organischen Chemie” (Houben-Weyl), volume E 8b, Georg Thieme Verlag Stuttgart, 1994, page 399 ff.; ibid, volume E7B, Georg Thieme Verlag Stuttgart, 1992, page 286 ff.; in “Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles and Condensed Rings”, Editor R. H. Wiley, Interscience Publishers, John Wiley & Sons, New York, 1967, page 1 ff.; or in “Comprehensive Heterocyclic Chemistry”, Editors A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1987, or by derivatisation according to known standard methods as described, for example, in “Advanced Organic Chemistry, Third Edition, Editor J. March, John Wiley & Sons, New York, 1985; in “Comprehensive Organic Transformations”, Editor R. C. Larock, VCH Publishers, Inc., New York, 1989; or in “Comprehensive Organic Functional Group Transformations”, Editors A. R. Katritzky, 0. Meth-Cohn, C. W. Rees, Pergamon Press, Oxford, 1995, or as described in the Patent Specifications EP-A-0 361 114, U.S. Pat. No. 5,032,165, WO 92/02509, WO 92/06962, WO 95/33728 and WO 96/01254.

The end products of formula I can be isolated in conventional manner by concentration or evaporation of the solvent and purified by recrystallisation or trituration of the solid residue in solvents in which they are not readily soluble, such as ethers, aromatic hydrocarbons or chlorinated hydrocarbons, by distillation or by means of column chromatography and a suitable eluant. The sequence in which it is advantageous for certain reactions to be carried out so as to avoid possible secondary reactions will also be familiar to the person skilled in the art. Unless the synthesis is specifically aimed at the isolation of pure isomers, the product may be obtained in the form of a mixture of two or more isomers. The isomers can be separated according to methods known per se.

For the use according to the invention of the compounds of formula I or of compositions comprising them, there come into consideration all methods of application customary in agriculture, for example pre-emergence application, post-emergence application and seed dressing, and also various methods and techniques such as, for example, the controlled release of active ingredient. For that purpose a solution of the active ingredient is applied to mineral granule carriers or polymerised granules (urea/formaidehyde) and dried. If required, it is also possible to apply a coating (coated granules), which allows the active ingredient to be released in metered amounts over a specific period of time.

The compounds of formula I may be used in unmodified form, that is to say as obtained in the synthesising process, but they are preferably formulated in customary manner together with the adjuvants conventionally employed in formulation technology, for example into emulsifiable concentrates, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules or microcapsules. Such formulations are described, for example, in WO 97/34485, pages 9 to 13. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, wetting, scattering or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.

The formulations, that is to say the compositions, preparations or mixtures comprising the compound (active ingredient) of formula I or at least one compound of formula I and, usually, one or more solid or liquid formulation adjuvants, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients with the formulation adjuvants, for example solvents or solid carriers. Surface-active compounds (surfactants) may also be used in addition in the preparation of the formulations. Examples of solvents and solid carriers are given, for example, in WO 97/34485, page 6.

Depending on the nature of the compound of formula I to be formulated, suitable surface-active compounds are non-ionic, cationic and/or anionic surfactants and surfactant mixtures having good emulsifying, dispersing and wetting properties. Examples of suitable anionic, non-ionic and cationic surfactants are listed, for example, in WO 97/34485, pages 7 and 8. In addition, the surfactants conventionally employed in formulation technology, which are described in, inter alia, uMcCutcheon's Detergents and Emulsifiers Annual” MC Publishing Corp., Ridgewood New Jersey, 1981, Stache, H., “Tensid-Taschenbuch”, Carl Hanser Verlag, Munich/Vienna 1981, and M. and J. Ash, “Encyclopedia of Surfactants”, Vol. I-III, Chemical Publishing Co., New York, 1980-81, are also suitable for the preparation of the herbicidal compositions according to the invention.

The herbicidal formulations generally contain from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of herbicide, from 1 to 99.9% by weight, especially from 5 to 99.8% by weight, of a solid or liquid formulation adjuvant, and from 0 to 25% by weight, especially from 0.1 to 25% by weight, of a surfactant. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations. The compositions may also comprise further ingredients, such as stabilisers, for example vegetable oils or epoxidised vegetable oils (epoxidised coconut oil, rape oil or soybean oil), anti-foams, for example silicone oil, preservatives, viscosity regulators, binders, tackifiers, and also fertilisers or other active ingredients.

The compounds of formula I can be used successfully either in the form of a mixture comprising the isomers IW1a and IW1b or in the form of pure isomer IW1a or IW1b, generally on plants or the locus thereof, at rates of application of from 0.001 to 4 kg/ha, especially from 0.005 to 2 kg/ha. The concentration required to achieve the desired effect can be determined by experiment. It is dependent on the nature of the action, the stage of development of the cultivated plant and of the weed and on the application (place, time, method) and may vary within wide limits as a function of those parameters.

The compounds of formula I and, generally, the isomers of formula 1a especially, are distinguished by herbicidal and growth-inhibiting properties, allowing them to be used in crops of useful plants, especially cereals, cotton, soybeans, sugar beet, sugar cane, plantation crops, rape, maize and rice, and also for non-selective weed control.

“Crops” is to be understood as meaning also crops that have been made tolerant to herbicides or classes of herbicides as a result of conventional methods of breeding or genetic techniques. The weeds to be controlled may be either monocotyledonous or dicotyledonous weeds, such as, for example, Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Phaseolus, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum halepense, Rottboellia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola and Veronica.

The following Examples further illustrate but do not limit the invention.

PREPARATION EXAMPLES Example P1

3-Fluoro-5-chloro-2-pyridinecarboxylic Acid Ethyl Ester

An autoclave is charged with 31.4 g of 2,5-dichloro-3-fluoropyridine, 400 ml of dry ethanol, 27.8 ml of triethylamine and 3.5 g of palladium bis(triphenylphosphine) dichloride (PdCl₂(PPh₃)₂) and then a pressure of 180 bars is applied with carbon monoxide. The mixture is maintained at 90° C. for 4 days. After cooling and releasing the pressure, a further 3.5 g of PdCl₂(PPh₃)₂ are added, a pressure of 130 bars is applied with carbon monoxide, and the mixture is maintained at 90° C. for 3 days, after which it is cooled to 25° C., the pressure is released and the mixture is discharged. After concentration in vacuo, absorption from ethyl acetate onto silica gel is carried out. The silica gel is applied to a flash chromatography column (silica gel) and then eluted with n-hexanelethyl acetate 3/1. 24.3 g of the desired target compound having a melting point of 48-50° C. are obtained.

Example P2

3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic Acid Ethyl Ester

An autoclave is charged with 200 g of 2,3-dichloro-5-trifluoromethylpyridine, 1.85 liters of ethanol, 260 ml of triethylamine and 6.5 g of palladium bis(triphenylphosphine) dichloride (PdCl₂(PPh₃)₂). At 25° C. a pressure of 110 bars is then applied with carbon monoxide and the mixture is maintained at 110° C. for 24 hours. After cooling to 25° C., the crude mixture is concentrated to a thick slurry, which is then partitioned between dilute sodium chloride solution and ethyl acetate. After extraction by shaking, and separation of the phases, the ethyl acetate phase is washed with water, dried over sodium sulfate and concentrated to dryness. The crude product is distilled under a high vacuum of 0.035 mbar. 200 g of the desired product are obtained in the form of a yellow oil having a boiling point of 67-70° C./0.035 mbar (yield 85% of the theoretical yield).

Example P3

3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic Acid

423 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid ethyl ester (Example P2) is placed in a mixture of 800 ml of water and 160 ml of ethanol. 800 ml of a 2N sodium hydroxide solution are added dropwise at below 35° C. After 3 hours, the mixture is washed twice with dichloromethane and then rendered acidic with excess concentrated hydrochloric acid while cooling with an ice-bath. The resulting slurry is filtered, washed with water and dried in vacuo. 318 g of the desired product are obtained in the form of a white solid having a melting point of 135° C. (decomposition).

Example P4

3-Fluoro-5-chlorotyridine-2-carboxylic Acid

70 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid ethyl ester (Example P1) are placed in 105 ml of dimethyl sulfoxide (DMSO). 230 ml of a 2N sodium hydroxide solution are added dropwise at 40° C. over a period of 30 minutes. The resulting yellow suspension is introduced into a mixture of 2 liters of ice-water and 400 ml of 2N hydrochloric acid. After subsequently stirring for 20 minutes, the mixture is filtered and the filtration residue is washed twice with water. 56.4 g of the desired target compound are obtained in the form of a white solid.

¹H-NMR (DMSO-D₆): 13.79 ppm (broad signal, 1H); 8.60 ppm (d, 1H); 8.27 ppm (dxd, 1H).

Example P5

3-Chloro-5-trifluoromethyl-2-pyridinecarboxylic Acid Chloride

89.3 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid (Example P3) are slowly heated to reflux with 60 ml of thionyl chloride and the mixture is then stirred at that temperature for 4 hours, after which it is cooled to 25° C. and concentrated to dryness in vacuo. Twice, toluene is added and the mixture is again concentrated to dryness. 94.0 g of the desired product are obtained in the form of a yellow residue.

¹H-NMR (CDCl₃): 8.91 ppm (d, 1H); 8.13 ppm (d, 1H).

Example P6

3-Fluoro-5-chloro-2-pyridinecarboxylic Acid Chloride

71.38 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid (Example P4) are placed in a round-bottomed flask and heated to 90° C. 59 ml of thionyl chloride are added dropwise from a dropping funnel over a period of 30 minutes, and the gas formed is introduced into sodium hydroxide solution. Stirring is then carried out for 5 hours at 100° C., after which the thionyl chloride is distilled off at normal pressure. After the addition of 50 ml of dry toluene, 20 ml thereof are distilled off. The resulting solution is poured into 200 ml of n-hexane and stirred overnight. After cooling in an ice-bath, the mixture is filtered and the filtration residue is washed twice with n-hexane. 68.7 g of the desired compound are obtained in the form of a brown solid.

¹H-NMR (CDCl₃): 8.60 ppm (d, 1H); 7.69 ppm (dxd, 1H).

Example P7

5-Chloro-3-fluoro-2-pyridinecarbaldehyde

110 g of 5-chloro-3-fluoro-2-pyridinecarboxylic acid ethyl ester (Example P1) are dissolved in 180 ml of tert-butanol. 27.4 g of sodium borohydride (NaBH₄, 97%) are added to the slightly brown solution, in the course of which a weak exothermic reaction is observed. By cooling occasionally with an ice-bath, the internal temperature is maintained below 30° C. The exothermic reaction has subsided after 1½ hours. The reaction mixture is then stirred overnight at 22° C. and subsequently cold water is added slowly, while stirring well. Extraction is carried out with diethyl ether, and the combined ethereal phases are washed with dilute sodium hydrogen carbonate solution and brine, dried over sodium sulfate, filtered and concentrated in vacuo. 58 g of a tacky solid are isolated. After digestion with n-hexane/-diethyl ether 50/1 and drying in vacuo, 48.6 g of a yellow solid are obtained having an R_(f) value on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate 1/1 (v/v)) of 0.40.

160.7 g of active manganese(IV) oxide (90%) are added to 22.4 g of the alcohol obtained as intermediate in 300 ml of methylene chloride, and a slight exothermic reaction can be detected. After stirring for 3 hours, the mixture is filtered over Hyflo and the filtrate is concentrated in vacuo. The residue (20 g) is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)). In that manner 11.0 g of the desired target compound are obtained in the form of a white solid having a melting point of 70-72° C. The R_(f) value of the product on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate 3/1 (v/v)) is 0.61.

Example P8

3-Chloro-5-trifluoromethyl-2-acetylpyridine

55.3 ml of malonic acid dimethyl ester are stirred with 129 ml of triethylamine and 24.9 g of anhydrous magnesium chloride for 2 hours in 250 ml of dry toluene. With the exothermic reaction, the reaction temperature rises to 45° C. At 25° C. 94.0 g of 3-chloro-5-trifluoromethyl-2-pyridinecarboxylic acid chloride (Example P5) in 150 ml of toluene are added dropwise thereto and the reaction mixture is further stirred overnight. An excess of concentrated hydrochloric acid is then added dropwise, and the mixture is diluted with water and extracted with ethyl acetate. The organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to yield 142 g of a red oil which is slowly introduced into a mixture of 20 ml of water and 400 ml of dimethyl sulfoxide, which is under gentle reflux by means of an oil bath of a temperature of 150° C. When the evolution of gas can no longer be detected, water is added and extraction is carried out with ether. The combined ethereal phases are washed with water, dried over sodium sulfate, filtered and concentrated. The residue is purified by means of column chromatography (silica gel; eluant: n-hexane/ethyl acetate 15/1 (v/v)), yielding 61 g of the desired product in the form of a yellow oil (70% of the theoretical yield).

¹H-NMR (CDCl₃): 8.81 ppm (d, 1H); 8.05 ppm (d, 1H); 2.72 ppm (s, 3H).

Example P9

1-(3-Chloro-5-trifluoromethyl-2-pyridyl)-3-dimethylamino-2-propen-1-one

5.0 g of 3-chloro-5-trifluoromethyl-2-acetylpyridine (Example P8) are introduced into 30 ml of toluene and 3.60 ml of N,N-dimethylformamide-dimethylacetal are added. The resulting yellow solution is stirred overnight at 100° C. After cooling to 25° C., the mixture is concentrated to dryness in vacuo, yielding 6.17 g of the desired target compound in the form of a dark-yellow oil which later solidifies.

¹H-NMR (CDCl₃): 8.74 ppm (d, 1H); 7.98 ppm (d, 1H); 7.92 ppm (broad signal, 1H); 5.54 ppm (broad d, 1H); 3.17 ppm (broad signal, 3H); 2.94 ppm (broad signal, 3H).

Example P10

3-(3.5-Dichloro-2-pyridyl)-5-trifluoromethyl-[1H]-pyrazole

15.8 g of 3,5-dichloro-2-acetylpyridine are introduced together with 12.0 ml of trifluoroethyl acetate into 125 ml of absolute ether. With stirring, the mixture is cooled using an ice-bath and 46.6 ml of, a 21% sodium ethanolate solution in ethanol are added dropwise. The ice-bath is then removed and the mixture is subsequently stirred overnight at 25° C. After cooling the reaction mixture in an ice-bath and adding dropwise 7.5 ml of glacial acetic acid, the mixture is concentrated in vacuo. 39.0 g of 1-(3,5-dichloro-2-pyridyl)-3-trifluoromethylpropane-1,3-dione are obtained, which can be used directly for the following cyclisation step.

39.0 g of 1-(3,5-dichloro-2-pyridyl)-3-trifluoromethylpropane-1,3-dione

are introduced into ethanol and 4.85 ml of hydrazine hydrate are slowly added. The reaction mixture is then heated at reflux with stirring. After one hour, the mixture is concentrated to dryness in vacuo and the residue is partitioned between dilute sodium hydrogen carbonate solution and ethyl acetate. After extraction by shaking, and separation of the phases, the organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. 22.25 g of a yellow oil are obtained, which is purified by means of flash chromatgraphy (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)) to yield 15.0 g of the desired product in the form of a yellow solid.

¹H-NMR (DMSO-D₆): 8.81 ppm (m, 1H); 8.64 ppm (m, 1H); 8.26 ppm (m, 1H); 7.45 ppm (broad signal, 1H).

Example P11

3-(3,5-Dichloro-2-pyridyl)-5-trifluoromethyl-1-methyl-[1H]-pyrazole and 5-(3,5-dichloro-2-pyridyl)-3-trifluoromethyl-1-methyl-[1H]-pyrazole

8.88 g of 3-(3,5-dichloro-2-pyridyl)-5-trifluoromethyl-[1H]-pyrazole (Example P10) are introduced into 35 ml of N-methylpyrrolidone. After the addition of 13.0 g of potassium carbonate, the mixture is stirred and heated to 55° C. 2.36 ml of methyl iodide in 5.0 ml of N-methylpyrrolidone are then slowly added dropwise. After subsequently stirring for 2 hours, diethyl ether and water are added, the mixture is extracted by shaking and the organic phase is separated off. The separated ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product is purified by means of flash chromatography (silica gel; eluant: toluene/ethyl acetate 100/1). First of all 3.96 g of the 5-pyridylpyrazole isomer (yield 42%) are isolated in the form of a yellow oil and then 1.96 g of the 3-pyridylpyrazole (yield 21%) are isolated in the form of a yellow solid. The R_(f) values of the 3- and 5-pyridylpyrazole isomers on silica gel 60 F₂₅₄ using toluene/ethyl acetate 30/1 as eluant (UV) are:

R_(f) value of 5-pyridylpyrazole: 0.50

R_(f) value of 3-pyridylpyrazole: 0.35

Example P12

3-(3,5-Dichloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole

2.0 g of 3-(3,5-dichloro-2-pyridyl)-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P11) are introduced into glacial acetic acid at 40° C. and, with stirring, chlorine gas is slowly passed over the solution. The reaction can be monitored analytically by means of thin-layer chromatography (silica gel 60 F₂₅₄, eluant: n-hexanelethyl acetate 4/1, UV). Once starting material can no longer be detected, glacial acetic acid is removed in vacuo and the residue is partitioned between dilute aqueous sodium hydroxide solution and ethyl acetate. After extraction by shaking, the separated organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated. The yellow oil is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 5/1). 1.6 g of of the desired compound are obtained in the form of a yellow oil (70% of the theoretical yield).

¹H-NMR (DMSO-D₆): 8.80 ppm (d, 1H); 8.48 ppm (d, 1H); 4.11 ppm (s, 3H).

The 5-pyridylpyrazole isomer is obtained in an analogous manner in a 90% yield (crude). ¹H-NMR (CDCl₃): 8.66 ppm (d, 1H); 7.95 ppm (d, 1H); 3.83 ppm (s, 3H).

Example P13

3-(3-Fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole

110.6 g of malonic acid monomethyl ester•potassium salt are introduced into 500 ml of absolute acetonitrile. With stirring, the mixture is cooled in an ice-bath and 109 ml of triethylamine are added dropwise. 84.3 g of anhydrous magnesium chloride are then added. A slight exothermic reaction is observed. After removal of the ice-bath, the mixture is stirred for 2 hours at 25° C. After cooling again in an ice-bath, 68.7 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid chloride (Example P6) are added in several portions and 300 ml of absolute acetonitrile are added. A thick slurry gradually forms. The cooling bath is removed and the slurry is then stirred for 5 hours. The reaction mixture is subsequently poured into 3 liters of ice-water and 200 ml of concentrated hydrochloric acid, and then stirred for 15 minutes and extracted with ethyl acetate. The organic phase is washed with water and brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. 110 g of a brown oil are obtained, which is used directly for the next reaction step.

For that reaction step, the brown oil obtained above is introduced at 25° C. into a solution of 20.5 ml of methyl hydrazine in 300 ml of glacial acetic acid and then stirred for 2 hours at 85° C. After the resulting brown suspension has been cooled to 25° C. it is introduced in portions into 2.5 liters of ice-water, stirred for 1 hour, filtered and washed with water and n-hexane. After drying at 60° C. in vacuo, 65.8 g of the desired title compound having a melting point of 195-199° C. are obtained.

Example P14

3-(3-Fluoro-5-chloro-2-pyridyl)-5-difluoromethoxy-1-methyl-[1H]-pyrazole

46.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) and 84 g of potassium carbonate are introduced into 250 ml of dry dimethylformamide and heated to 85° C. While stirring well, Freon 22 (chlorodifluoromethane) is then introduced for a period of 2 hours. TLC analysis of a worked-up sample (silica gel 60 F2s; eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1, UV) shows that there is no starting material present. The reaction mixture is partitioned between water and diethyl ether (foaming occurs on the addition of water). After extraction by shaking, and separation of the phases, the ethereal phase is washed twice with water and once with brine. After drying the organic phase over sodium sulfate and filtration, concentration in vacuo is carried out and the residue is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 22.0 g of the desired title compound are obtained in the form of a light-yellow solid.

¹H-NMR (CDCl₃): 8.51 ppm (broad signal, 1H); 7.56 ppm (dxd, 1H); 6.61 ppm (t, 1H); 6.53 ppm (d, 1H); 3.89 ppm (s, 3H).

Example P15

3-(3-Fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluorometho)-1-methyl-[1H]-pyrazole

17.92 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P14) are introduced into 60 ml of glacial acetic acid together with 10.6 g of sodium acetate. With stirring, the mixture is heated to 60° C. and a saturated solution of chlorine in glacial acetic acid is added until TLC analysis of a worked-up sample shows that the reaction is complete (silica gel 60 F₂₅₄; eluant: n-hexane/ethyl acetate 2/1; UV, R₁ value of the starting material 0.34; R₁ value of the product 0.48). The mixture is then concentrated to dryness in vacuo and the residue obtained is partitioned between sodium hydrogen carbonate solution and ethyl acetate. The organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness by evaporation in vacuo. 19.8 g of the desired target compound (pure according to TLC) having a melting point of 95-96° C. are obtained.

Example P16

3-(3-Fluoro-5-chloro-2-pyridyl)-4-formyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole

With cooling in an ice-bath, 2.41 ml of phosphorus oxychloride are introduced into 5 ml of N,N-dimethylformamide and the mixture is then stirred for 2 hours at 25° C. The mixture is then added dropwise at 80° C. to 5.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) in 15 ml of N,N-dimethylformamide over a period of 30 minutes. After subsequently stirring for 1.5 hours at 80° C., the mixture is cooled to 25° C. and ice and then water are added and extraction is carried out with diethyl ether. The organic phase is washed with water and dried over sodium sulfate to yield 1.1 g of a yellow solid as intermediate. The solid is introduced together with 1.72 g of pulverised anhydrous potassium carbonate into 10 ml of dry N,N-dimethylformamide. While stirring well, the mixture is heated to 75° C. and freon 22 (CHClF₂) is slowly introduced for a period of 7 hours. The mixture is then cooled to 25° C. and taken up in diethyl ether. The ethereal phase is washed with water and then with brine, dried over sodium sulfate, filtered and concentrated. 1.50 g of crude product are obtained in the form of a brown solid, which is purified using a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 4/1 (v/v)). In that manner 0.14 g of the desired target compound is obtained in the form of a yellow solid having a melting point of 111-116° C.

Example P17

3-(3-Fluoro-5-chloro-2-pyridyl)-4-difluoromethyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole

0.13 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-formyl-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P16) is introduced into 3.0 ml of dry 1,2-dichlorethane. With stirring, 0.11 ml of diethylamino-sulfur trifluoride (DAST) is added dropwise using a syringe, the reaction mixture taking on a dark colour. The mixture is then stirred for 1 hour at 50° C. The reaction solution is cooled to 25° C. and applied directly to a flash chromatography column (silica gel) and eluted with n-hexane/ethyl acetate 5/1 (v/v). 0.07 g of the desired compound is obtained in the form of a light-yellow oil having a melting point of 79-81° C.

Example P18

3-(3-Fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazole

20.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) are introduced into 80 ml of tetrachloroethane. A total of 25.2 g of phosphorus oxybromide (POBr₃) is added in portions to the brown suspension. The mixture is then stirred for 2 hours at an internal temperature of 130° C., after which it is cooled and, with cooling with an ice-bath, 150 ml of a 2M sodium hydroxide solution are added dropwise. After the addition of diethyl ether and separation of the phases, the organic phase is washed in succession with water, dilute hydrochloric acid and brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. 19.94 g of a brown solid (crude product) are obtained, which is purified by means of digestion with 50 ml of n-hexane. 12.65 g of the desired compound are obtained in the form of a brown solid having a melting point of 110-111° C.

Example P19

5-(5-Chloro-3-fluoro-2-pyridyl)-2-methyl-[2H]-pyrazole-3-carboxylic Acid Ethyl Ester

5.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazole (Example P18) are introduced into an autoclave together with 7.2 ml of triethylamine, 0.48 g of bis-triphenylphosphinepalladium dichloride (PdCl₂(PPh₃)₂) and 70 ml of absolute ethanol. At 22° C. a pressure of 100 bar is applied with carbon monoxide and the reaction mixture is maintained at 100° C. for 48 hours. In the meantime a further 0.48 g of bis-triphenylphosphinepalladium dichloride is added, and the mixture is then cooled to 22° C. and the pressure is released. The reaction mixture is filtered over Hyflo and, after evaporating off the ethanol, taken up in ethyl acetate. The ethyl acetate phase is washed with dilute hydrochloric acid and then with brine, dried over sodium sulfate, filtered and finally concentrated to dryness in vacuo. 3.17 g of a brown solid are obtained, which is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 2.31 g of the desired title compound are obtained in the form of a light-yellow solid having a melting point of 117-118° C.

Example P20

5-(5-Chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic Acid Ethyl Ester

22.9 g of 5-(5-chloro-3-fluoro-2-pyridyl)-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester (Example P19) are introduced together with 19.9 g of sodium acetate into 300 ml of glacial acetic acid at a temperature of 65° C. With stirring, 6.3 g of chlorine gas are passed over the solution at that temperature in the course of 1 hour. The reaction mixture is then poured into 2.5 liters of ice-water and subsequently stirred for 20 minutes. The resulting precipitate is filtered off, washed with ice-water and then dried in vacuo at 50° C. 24.4 g of the desired title compound are obtained in the form of a yellow solid having a melting point of 77-79° C.

Example P21

5-(5-Chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic Acid

11.0 g of 5-(5-chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid ethyl ester (Example P20) are introduced into 60 ml of dimethyl sulfoxide at 22° C. With stirring, 25.9 ml of a 2N aqueous sodium hydroxide solution are added dropwise, in the course of which an exothermic reaction can be detected. After subsequently stirring for one hour, TLC analysis of a sample shows that all the starting material has reacted. The reaction mixture is introduced into 2 liters of ice-cold dilute hydrochloric acid, then stirred for 15 minutes and filtered over a paper filter. The filtration residue is washed with cold water and, after drying overnight at 60° C. in vacuo, 8.7 g of the desired title compound having a melting point of 230° C. (decomposition) are obtained.

The R_(f) value of the starting material on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.75; and the R_(f) value of the desired title compound is 0.36.

Example P22

3-(3-Fluoro-5-chloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole

8.63 g of 5-(5-chloro-3-fluoro-2-pyridyl)-4-chloro-2-methyl-[2H]-pyrazole-3-carboxylic acid (Example P21) are introduced into a fluorination unit with 27 g of hydrogen fluoride (HF), 16.2 g of sulfur tetrafluoride (SF₄) and 270 ml of methylene chloride. The mixture is maintained at 80° C. for 5 hours. It is then cooled to 22° C. and the SF₄ is removed by way of a gas destroying unit (argon stream) and the HF is removed using a water-jet vacuum. After the addition of methylene chloride, the reaction mixture is extracted three times with ice-water, and the organic phase is dried over sodium sulfate and then concentrated to dryness in vacuo together with 40 g of silica gel. After applying the silica gel to a flash chromatography column, elution is carried out with an n-hexane/ethyl acetate 5/1 (v/v) mixture. 5.48 g of the desired title compound are obtained in the form of a beige solid having a melting point of 76-78° C.

Example P23

3-(5,6-Dichloro-2-pyridyl)- and 3-(4,5-dichloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (isomers A and B)

20 ml of phosphorus oxychloride are heated to 90° C. With stirring, 10.37 g of 3-(5-chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P25) are introduced in several portions at that temperature and the mixture is then stirred for 1 hour at 90° C. The phosphorus oxychloride is then evaporated off in vacuo, the residue is taken up in diethyl ether and the ethereal phase is subsequently washed in succession with water, 0.5M sodium hydroxide solution and brine. After drying over sodium sulfate and filtering, concentration in vacuo is carried out and the residue obtained (8.93 g) is purified by column chromatography (silica gel; eluant: n-hexane/ethyl acetate 10/1). First 0.57 g of isomer B and then 5.11 g of isomer A are isolated in the form of a white solid.

On silica gel 60 F₂₅₄ using the eluant n-hexane/ethyl acetate 4/1 (v/v), the R_(f) value of isomer A is 0.31 and the R_(f) value of isomer B is 0.41.

The treatment of 6.3 g of 3-(5-chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole (Example P25) for 1 hour at 90° C. with 6.3 g of phosphorus pentachloride in 20 ml of phosphorus oxychloride yields, after working up as above, 4.36 g of isomer A and 1.01 g of isomer B.

Example P24

3-(3-Fluoro-5,6-dichloro-2-pyridyl-N-oxide)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole

1.5 g of 3-(3-fluoro-5,6-dichloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole are dissolved in 10 ml of 1,2-dichloroethane and 0.5 g of hydrogen peroxide/urea adduct is added. With cooling in an ice-bath, 0.66 ml of trifluoroacetic anhydride is then metered in using a syringe and the mixture is stirred at 22° C. for 3 hours. According to TLC analysis there is only partial reaction of the starting material. Consequently, 0.5 g of hydrogen peroxide/urea adduct and 0.66 ml of trifluoroacetic anhydride are added to the reaction mixture one after the other, in the manner described above, four times, followed each time by stirring for 3 hours at 22° C., in the course of which a yellow suspension is formed which is taken up in ethyl acetate. The organic phase is washed in succession with 1 N sodium hydroxide solution, water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product is purified by means of flash chromatography (silica gel; eluant: hexane/ethyl acetate 3/2). 0.25 g of the desired product is obtained in the form of yellow crystals having a melting point of 114-118° C.

Example P25

3-(5-Chloro-2-pyridyl-N-oxide)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole

6.82 g of 3-(5-chloro-2-pyridyl)-4-chloro-5-trifluoromethyl-1-methyl-[1H]-pyrazole are introduced into 30 ml of methylene chloride at 25° C. With stirring, 7.23 g of m-chloroperbenzoic acid are added. After 48 hours a further 2.50 g of m-chloroperbenzoic acid are added. After a further 24 hours the reaction mixture is taken up in ethyl acetate and extracted twice with dilute sodium hydroxide solution, then washed with brine, dried over sodium sulfate and concentrated. Chromatography is then carried out (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 6.31 g of the desired compound are isolated in the form of a white solid.

¹H-NMR (DMSO-D₆): 8.75 ppm (d, 1H); 7.66 ppm (d, 1H); 7.59 ppm (dxd, 1H); 4.08 ppm (s, 3H).

Starting from the S-(5-chloro-2-pyridyl)-4-chloro-3-trifluoromethyl-1-methyl-[1H]-pyrazole isomer, the 5- (5-chloro-2-pyridyl-N-oxide)-4-chloro-3-trifluoromethyl-1-methyl-[1H]-pyrazole isomer can be obtained in a yield of 70%.

Example P26

3-(3-Fluoro-5-chloro-2-pyridyl-N-oxide)-4-chloro-S-difluoromethoxy-1-methyl-[1H]-pyrazole

0.57 g of 3- (3-fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P15) is introduced into 5 ml of methylene chloride and 0.63 g of a 55% m-chloro- perbenzoic acid is added. After stirring for 4 days at 25° C., the crude mixture is taken up in ethyl acetate and washed in succession with sodium hydrogen carbonate solution, water and brine. After drying over sodium sulfate and filtering, concentration is carried out and the residue is purified by means of flash chromatography. 0.45 g of the desired target compound is obtained in the form of a white solid having a melting point of 115-120° C.

Example P27

3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol

1.0 g of 3-(3-fluoro-5-chloro-2-pyridyl-N-oxide)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P26) is introduced into 12 ml of dry N,N-dimethylformamide. With stirring and cooling with an ice-bath, 4.2 ml of trifluoroacetic anhydride are added dropwise from a syringe and the mixture is subsequently stirred overnight at 25° C. The mixture is then concentrated by evaporation in vacuo and the residue is partitioned between diethyl ether and water. After extraction by shaking, and separation of the phases, the ethereal phase is washed with dilute aqueous sodium hydrogen carbonate solution and brine, dried over sodium sulfate, filtered and concentrated. 1.23 g of a yellow oil are obtained, which is purified using a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 2/3 (v/v) and 1% glacial acetic acid). 0.59 g of the desired compound is obtained in the form of a yellow solid having a melting point of 126-128° C.

Example P28

5-(5-Chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic Acid

6.75 g of 5-(5-chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid ethyl ester are suspended in 40 ml of dimethyl sulfoxide. With occasional cooling in an ice-bath (internal temperature <30° C.), 14.3 ml of a 2N sodium hydroxide solution are added dropwise. The thick, yellowish-brown suspension is stirred at 22° C. for 2 hours. The suspension is then introduced into ice-water and adjusted to pH 1 with 2N hydrochloric acid. The resulting slurry is filtered, washed well with cold water and then dried in vacuo at 60° C. 5.97 g of the desired title compound are obtained in the form of a beige solid having a melting point of 194-196° C.

Example P29

5-(5-Chloro-3-fluoropyridin-2dl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic Acid Amide

3.0 g of 5-(5-chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid (Example P28) are introduced into 25 ml of 1,2-dichloroethane and, at 80° C., a total of 1.21 ml of thionyl chloride is added and the mixture is subsequently stirred for 5 hours at 80° C. The mixture is concentrated in vacuo, 20 ml of carbon tetrachloride are added three times and each time the mixture is concentrated to dryness by evaporation. The resulting acid chloride is introduced into 35 ml of tetrahydrofuran. With cooling in an ice-bath, ammonia gas is introduced. A brown precipitate forms. Stirring is carried out overnight at 22° C. The resulting suspension is introduced into five times its volume of ice-water. After then stirring briefly, filtration is carried out and the filtration residue is subsequently washed with cold water and dried in vacuo at 60° C. 2.0 g of the desired title compound are obtained in the form of a brown solid having a melting point of 201-204° C.

Example P30

5-Chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carbonitrile

1.82 g of 5-(5-chloro-3-fluoropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carboxylic acid amide (Example P29) are suspended in 20 ml of dioxane. With cooling with an ice-bath, first 1.65 ml of pyridine and then 1.44 ml of trifluoroacetic anhydride are added. After 5 minutes the cooling bath is removed and the mixture is subsequently stirred for 1 hour at 22° C. The brownish-red solution is diluted with diethyl ether and washed with 1 N hydrochloric acid and then with brine. The mixture is dried over sodium sulfate and filtered and then directly concentrated with twice the amount of silica gel. After application of the silica gel to a flash chromatography column, elution is carried out with n-hexane/ethyl acetate 4/1 (v/v). 1.60 g of the desired title compound are obtained in the form of a beige solid having a melting point of 144-146° C.

Example P31

3-(3-Fluoro-5-methyl-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole

2.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P15) are introduced into 6 ml of absolute dioxane. In order to remove the oxygen, gentle evacuation is carried out three times (water-jet pump) and the mixture is gassed with argon. 6.4 ml of a 2M solution of trimethylaiuminium in toluene and 0.10 g of tetrakistriphenylphosphinepalladium (Pd(PPh₃)₄) are added thereto. The mixture is heated to 90° C., with stirring, in an argon atmosphere. The next day the mixture is cooled to 22° C., a further 0.10 g of Pd(PPh₃)₄ and 6.4 ml of a 2M solution of trimethylaluminium in toluene are added and the mixture is stirred at 110° C. After 4 hours, TLC analysis of a worked-up sample shows that all the starting material has reacted. The reaction mixture is introduced carefully into cold, dilute hydrochloric acid and is then extracted with ethyl acetate. The combined organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated by evaporation in vacuo. The crude product obtained is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 1.36 g of the desired compound are obtained in the form of a yellow oil, which slowly crystallises; melting point 41-42° C.

The R_(f) value of the starting material on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate 2/1 (v/v)) is 0.37 and the R₁ value of the title compound is 0.15.

Example P32

3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-hydroxy-[1H]-2-pyridin-2-one

0.50 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1l]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) is introduced into 4 ml of 1,2-dichloroethane, and 0.15 g of hydrogen peroxide/urea adduct (30%) and 0.22 ml of trifluoroacetic anhydride are added. The mixture is stirred overnight at 22° C. and then a further 0.15 g of hydrogen peroxide/urea adduct is added together with 0.22 ml of trifluoroacetic anhydride. The mixture is subsequently stirred for 5 hours and then partitioned between ethyl acetate and dilute hydrochloric acid. The separated organic phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. 0.55 g of the desired compound is obtained in the form of a yellow resinous precipitate (crude product).

¹H-NMR (CDCl₃): 7.65 ppm (d, 1H); 6.74 ppm (t, 1H); 3.90 ppm (s, 3H).

Example P33

3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methoxy-[1H]-pyridin-2-one

0.20 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-hydroxy-[1H]-pyridin-2-one (Example P32) is introduced into 2 ml of N-methylpyrrolidone (NMP) at 22° C. and 0.16 g of anhydrous potassium carbonate is added. With stirring, 0.10 g of methyl iodide in 0.5 ml of NMP is then added dropwise. The reaction mixture is stirred for 2 hours at 22° C. and then partitioned between 20 ml of water and diethyl ether. The separated ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness by evaporation in vacuo. 0.13 g of the desired crude product is obtained in the form of a yellow oil which, after purification by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)), yields 0.08 g of pure product in the form of a colourless oil.

¹H-NMR (CDCl₃): 7.62 ppm (d, 1H); 6.74 ppm (t, 1H); 4.00 ppm (s, 3H); 3.90 ppm (s, 3H).

Example P34

3-(5-Chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic Acid Tert-Butyl Ester

32.3 g of diisopropylamine are introduced into 200 ml of tetrahydrofuran and, with cooling with a CO₂/acetone cooling bath, 200 ml of a 1.6M solution of n-butyllithium in hexane are added dropwise. 49.2 ml of propionic acid tert-butyl ester are then added dropwise at approximately −75° C. and the mixture is stirred at that temperature for 45 minutes. At approximately −75° C. a solution of 32.6 g of 3-fluoro-5-chloro-2-pyridinecarboxylic acid ethyl ester (Example P1) in 40 ml of tetrahydrofuran (THF) is then added dropwise and the mixture is stirred at that temperature for 1 hour, after which it is diluted with 250 ml of tert-butyl methyl ether. A mixture of 100 ml of water and 200 ml of glacial acetic acid is added, the phases are separated, the aqueous phase is extracted again, and the combined organic phases are washed with water. After drying over magnesium sulfate, filtration and concentration to dryness in vacuo are carried out. 51 g of the desired compound are obtained in the form of an oil (crude product).

The R_(f) value of the starting material on silica gel 60 F₂₅₄ (eluant: n-hexanelethyl acetate 3/1 (v/v)) is 0.46, and the R_(f) value of the product is 0.63.

Example P35

3-(5-Chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid

25.5 g of 3- (5-chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid tert-but yl ester (Example P34) are added dropwise to 30 ml of a 33% solution of hydrogen bromide (HBr) in glacial acetic acid to form a suspension. The mixture is subsequently stirred for 90 minutes and then introduced into 300 ml of ice-water. The resulting precipitate is filtered off, washed with water and dried. 15.9 g of the desired title compound are obtained in the form of a solid having a melting point of 101-102° C.

Example P36

2-Chloro-1-(5-chloro-3-fluoropyridin-2-yl)- propan-1-one

20.8 g of 3-(5-chloro-3-fluoropyridin-2-yl)-2-methyl-3-oxopropionic acid (Example P35) are introduced into 125 ml of glacial acetic acid. 6.3 g of chlorine gas are introduced into the solution in the course of 1 hour . The mixture is then poured into 700 ml of water and extracted with tert-butyl methyl ether. The combined ethereal phases a rewashed with water and dried over magnesium sulfate, filtered and concentrated by evaporation in vacuo. The crude product is dissolved in 180 ml of tert-butyl methyl ether, 45 g of silica gel are added and the mixture is stirred for 30 minutes, in the course of which the evolution of gas observed initially comes to a halt. The silica gel is then filtered off and subsequently washed and the combined ethereal phases are concentrated to dryness in vacuo. 20.1 g of an oily crude product are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 411 (v/v)). 17.0 g of the desired title compound are obtained in the form of a solid having a melting point of 29-32° C.

Example P37

5-(5-Chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6-dihydro-[1,3,4]-thiadiazine-2-thione

19.1 ml of a 4N sodium hydroxide solution and 3.5 g of methyl hydrazine are introduced into 76 ml of ethanol. At an internal temperature of <5° C., 4.5 ml of carbon disulfide are added dropwise with stirring, and the mixture is then stirred for 30 minutes. 17.0 g of 2-chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one (Example P36) are subsequently added in the course of 15 minutes at an internal temperature of <5° C. The temperature is then allowed to rise to 22° C. and the mixture is subsequently stirred for 30 minutes. TLC analysis (silica gel 60 F₂₅₄; eluant: n-hexane/ethyl acetate, UV) of a worked-up sample shows that starting material is no longer present. 2.5 ml of a concentrated hydrochloric acid solution are then added dropwise to form a yellow precipitate. Stirring is carried out for 1 hour and the mixture is then poured into water and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 20.3 g of the desired title compound are obtained in the form of a solid having a melting point of 107-112° C.

Example P38

5-Chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine

21.6 g of crude 5-(5-chloro-3-fluoropyridin-2-yl)-3,6-dimethyl-3,6-dihydro-[1.3.4]-thiadiazine-2-thione (Example P37) are introduced into 70 ml of tert-butanol, 19.1 g of triphenylphosphine are added and the mixture is stirred at an internal temperature of 65° C. for approximately 15 minutes, a clear solution forming. After cooling to 22° C., a suspension again forms, to which 8.2 g of potassium tert-butanolate are added in portions at an internal temperature of <40° C. (cooling with an ice-bath). The mixture is then stirred overnight, subsequently poured into 600 ml of water, stirred, filtered and washed, and the aqueous phase is extracted thoroughly with tert-butyl methyl ether. The aqueous phase is rendered strongly acidic with concentrated hydrochloric acid and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 6.8 g of a crude intermediate are obtained.

1.9 g of the intermediate are dissolved in 10 ml of dimethylformamide (DMF) and 2.2 g of potassium carbonate are added. 0.5 ml of methyl iodide in 2 ml of DMF is then added dropwise. The mixture is subsequently stirred at 22° C. for 5 hours, poured into 120 ml of ice-water, and extracted with diethyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. 1.8 g of an oil are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 1.3 g of the desired title compound are obtained in the form of a solid having a melting point of 61-64° C.

Example P39

5-Chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluororyridine

2.1 g of 5chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine (Example P38) are dissolved in 40 ml of methylene chloride, and 2.84 g of 70% meta-chloroperbenzoic acid are added in portions. The mixture is then stirred for 4 hours at 22° C. and subsequently stirred with 1N sodium hydrogen carbonate solution for 30 minutes. The organic phase is separated off, washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. 1.7 g of a solid are obtained, which is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 0.80 g of the desired sulfone having a melting point of 145-147° C. and 0.70 g of the sulfoxide having a melting point of 112-114° C. are obtained.

Example P40

5-Chloro-3-fluoro-2-(5-methanesulfonyl-1.4-dimethyl-[1H]-pyrazol-3-yl)-pyridine-1-oxide

5.3 g of 5-chloro-2-(1,4-dimethyl-5-methylsulfanyl-[1H]-pyrazol-3-yl)-3-fluoropyridine (Example P39) are dissolved in 50 ml of methylene chloride. With stirring, 19.2 g of 70% m-chloroperbenzoic acid (MCPBA) are introduced in portions at 22° C. with exothermic reaction. The mixture is then stirred overnight at 22° C. The next day, a further 4.9 g of MCPBA are added and the mixture is stirred overnight. The mixture is subsequently extracted with dilute sodium hydrogen carbonate solution and then with sodium thiosulfate solution. The extract is dried over magnesium sulfate and then filtered and concentrated to dryness in vacuo. The crude product (6 g) is purified over silica gel using ethyl acetate as eluant. 3.6 g of the desired title compound having a melting point of 174-176° C. are obtained.

Example P41

3-Chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-[1H]-pyridin-2-one

2.6 go 5-chloro-3-fluoro-2-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-pyridine-1-oxide (Example P40) are introduced into 35 ml of dry dimethylformamide. At a temperature of 10° C., 16.8 g of trifluoroacetic anhydride are added dropwise and the mixture is then stirred overnight at 22° C., subsequently poured into 2 liters of ice-water and extracted with tert-butyl methyl ether. After drying over magnesium sulfate, filtering and concentrating to dryness by evaporation in vacuo, 1.8 g of the desired compound are obtained as crude product, which can be used directly in the next step.

Example P42

3-Chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-1-propyn-2-yl-[1H]-pyridin-2-one

1.8 g of 3-chloro-5-fluoro-6-(5-methanesulfonyl-1,4-dimethyl-[1H]-pyrazol-3-yl)-[1H]-pyridin-2-one (Example P41) are dissolved in 10 ml of dimethyl sulfoxide and 3.0 ml of a 2N aqueous sodium hydroxide solution are added (slightly exothermic reaction). After subsequently stirring for 30 minutes at 22° C., 0.46 ml of propargyl bromide is added dropwise and the mixture is further stirred overnight at 22° C. The reaction mixture is then introduced into 120 ml of ice-water, filtered, and washed with water. It is taken up in ethyl acetate, dried over magnesium sulfate, filtered and concentrated to dryness by evaporation in vacuo. The crude product is purified by means of silica gel chromatography (eluant: n-hexane/ethyl acetate 1/1 (v/v)). 0.74 g of the desired title compound, which still contains 20% of the isomeric 0-propargyl derivative, is obtained; m.p. 189-192° C.

The R_(f) value of the title compound on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.28, the R_(f) value of the O-propargyl isomer is 0.55, and the R_(f) value of the starting compound is 0.05.

Example P43

5-(5-Chloro-3-fluoro-1-methyl-6-oxo-1,6-dihydropyridin-2-yl)-2,4-dimethyl-[2H]-pyrazole-3-carbonitrile

1.54 g of 3-chloro-6-(1,4-dimethyl-5-cyano-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol are introduced into a mixture of 20 ml of absolute 1,2-dimethoxyethane and 5 ml of absolute dimethylformamide at 22° C. With stirring, first 1.20 g of lithium bromide are added and then, 10 minutes later, in portions, 0.28 g of a 60% sodium hydride dispersion in oil. After a further 10 minutes, 0.86 ml of methyl iodide is added, after which the mixture is stirred overnight at 90° C. The mixture is then cooled to 22° C., carefully poured into dilute hydrochloric acid, and extracted with diethyl ether. The combined ethereal phases are washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo together with 4 g of silica gel. The silica gel is applied to a flash chromatography column and fractionated by means of gradient elution using n-hexane/ethyl acetate 3/1 to 1/1 (v/v). 0.68 g of the desired compound is obtained in the form of a white solid having a melting point of 190-191° C.

Example P44

1-Allyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one

1.50 g of 3-(3-fluoro-5-chloro-6-hydroxy-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P27) are suspended in a dry mixture of 16 ml of dimethoxyethane and 4 ml of N,N-dimethylformamide (DMF). With stirring, a total of 0.20 g of a 55% sodium hydride dispersion is added, in portions, at 25° C. The suspension is subsequently stirred for ten minutes, 0.79 g of anhydrous lithium bromide is then added and, after a further fifteen minutes' stirring, 0.77 ml of allyl bromide is added dropwise. The mixture is subsequently stirred overnight at 65° C. The next day, TLC analysis of a worked-up sample shows that starting material is no longer present. The reaction mixture is cooled to 2500 and partitioned between dilute hydrochloric acid and tert-butyl methyl ether. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo together with 5 g of silica gel. The silica gel is applied to a flash chromatography column and chromatography is carried out (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 0.95 g of the target compound is obtained in the form of a slightly yellowish-brown-coloured oil, the R_(f) value of which on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.33.

Example P45

1-Ethyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one

1.5 g of 3-(3-fluoro-5-chloro-6-hydroxy-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P27) are introduced into 6 ml of dimethyl sulfoxide (DMSO). 2.5 ml of a 2N aqueous sodium hydroxide solution are added thereto. 0.78 g of ethyl iodide in 2 ml of DMSO is then added dropwise, with stirring, and the mixture is further stirred overnight at 70° C. The next day, the reaction mixture is partitioned between dilute hydrochloric acid and diethyl ether. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. Finally, the residue is purified over a flash chromatography column (silica gel; elution gradient: n-hexane/ethyl acetate 4/1 to 1/1 (v/v)). 0.54 g of the desired target compound is obtained in the form of a yellow oil having an R_(f) value of 0.17 on silica gel 60 F₂₅₄ (eluant: n-hexane/-ethyl acetate 2/1 (v/v)).

Example P46

3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid benzyl ester

10.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are introduced into a mixture of 100 ml of dimethoxyethane and 25 ml of dimethylformamide at 22° C. 1.22 g of sodium hydride (60%, moistened in oil) are then added in portions, evolution of gas being observed. After subsequently stirring for 15 minutes at 22° C., 5.3 g of dry lithium bromide are added (slightly exothermic reaction) and, after 10 minutes, 9.6 ml of bromoacetic acid benzyl ester are added. The mixture is then stirred for 5 hours at 75° C. After cooling to 22° C., the mixture is taken up in ethyl acetate, washed with dilute hydrochloric acid and then with brine, subsequently dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. 24.3 g of a yellow oil are obtained, which is purified by means of flash chromatography (silica gel; eluant: n-hexane/-ethyl acetate 2/1 (v/v)). 7.67 g of the desired compound are obtained in the form of a yellow oil which crystallises on being left to stand; m.p. 83-85° C.

The R_(f) value of the starting material on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate/-glacial acetic acid 20/20/1 (v/v/v)) is 0.45, and the R_(f) value of the title compound is 0.60. The isomeric O-alkyl derivative is isolated as secondary product.

Example P47

3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid

6.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid benzyl ester (Example P46) are hydrogenated at normal pressure and 22° C. with 0.35 g of 5% palladium-on-active carbon in 90 ml of tetrahydrofuran (THF). After 2.5 hours, the reaction mixture is filtered over Hyflo and washed with THF. 5.11 g of the desired title compound are obtained in the form of a colourless resin, which solidifies on being left to stand.

¹H-NMR (CDCl₃): 7.58 ppm (d, 1H); 6.66 ppm (t, 1H); 4.73 ppm (s, 2H); 3.77 ppm (s, 3H).

Example P48

3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid imidazolide

2.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid (Example P47) are suspended in 20 ml of 1,2-dichloroethane. With stirring, 0.92 g of 1,1′-carbonyidiimidazole is added at 22° C. The mixture is stirred overnight and the resulting solution is concentrated to dryness by evaporation in vacuo. 2.40 g of the desired title compound are obtained in the form of a beige solid, which contains 20% by weight imidazole.

¹H-NMR (DMSO-D₆): 8.51 ppm (s, 1H); 8.41 ppm (d, 1H); 7.77 ppm (m, 1H); 7.33 ppm (t, 1H); 7.13 ppm (m, 1H); 5.46 ppm (s, 2H); 3.60 ppm (s, 3H).

Example P49

3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic Acid Diethylamide

1.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid (Example P47) is introduced into 8 ml of 1,2-dichloroethane. 0.50 g of carbonyidiimidazole is added to the white suspension and the mixture is stirred for one hour at 22° C., in the course of which all undissolved components dissolve. 0.39 ml of diethylamine is then added and the mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed in succession with dilute sodium hydrogen carbonate solution, dilute hydrochloric acid and brine. After drying over sodium sulfate, filtration is carried out and the residue is concentrated to dryness in vacuo. 1.20 g of a yellow oil is obtained which is purified over a flash chromatography column (silica gel;

eluant: ethyl acetate). 1.27 g of the desired title compound are obtained in the form of a colourless resin.

¹H-NMR (CDCl₃): 7.61 ppm (d, 1H); 6.72 ppm (t, 1H); 4.99 ppm (s, 2H); 3.82 ppm (s, 3H); 3.27 ppm (m, 4H); 1.13 ppm (t, 3H); 1.04 ppm (t, 3H).

Example P50

3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl-acetic Acid Allylamide

1.0 g of 3-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-acetic acid imidazolide (crude product) (Example P48) is introduced into 6 ml of 1,2-dichloroethane at 22° C. After the addition of 0.21 ml of allylamine, the mixture is stirred overnight and then taken up in ethyl acetate and washed in succession with dilute sodium hydroxide solution, brine, dilute hydrochloric acid and brine. Drying over sodium sulfate, filtration and concentration by evaporation in vacuo yield 0.77 g of the desired compound in the form of a white solid having a melting point of 146-148° C.

Example P51

3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylmethyl)-[1H]-pyridin-2-one

4.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are introduced into a mixture of 40 ml of dry dimethoxyethane and 10 ml of dry dimethylformamide at 22° C., and 0.49 g of a 60% sodium hydride (NaH) dispersion in hexane is added. After 15 minutes' stirring, 2.12 g of lithium bromide are added and the mixture is subsequently stirred for 10 minutes. 2.0 ml of chlorodimethyl sulfide are then added and the mixture is further stirred overnight at 70° C. After cooling to 22° C., a sample is removed and analysed in a thin-layer chromatogram (TLC). Since starting material is still present, a further 0.30 g of sodium hydride dispersion (60%) and 0.60 ml of chlorodimethyl sulfide are added and the mixture is then again stirred overnight at 70° C. After cooling to 22° C., the mixture is taken up in ethyl acetate, and dilute hydrochloric acid is added carefully. After extraction by shaking, and separation of the phases, the ethyl acetate phase is washed with brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. The crude product is purified over silica gel (eluant: n-hexane/ethyl acetate 2/1 (v/v)). First 0.51 g of the 0-alkyl isomer is eluted and then 3.04 g of the desired title compound in the form of a yellow oil, which slowly crystallises out.

The R_(f) value of the title compound on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1 (v/v/v)) is 0.37, the R_(f) value of the 0-alkyl isomer is 0.70 and the R_(f) value of the starting material is 0.31.

Example P52

3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfonylmethyl)-[1H]-pyridin-2-one

1.97 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylmethyl)-[1H]-pyridin-2-one (Example P51) are introduced into 25 ml of dichloroethane at 22° C. 3.75 g of m-chloroperbenzoic acid (70%) are added to the yellow solution with a slight exothermic reaction. The mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed with dilute sodium hydroxide solution and then with brine. After drying over sodium sulfate, filtration is carried out followed by concentration to dryness in vacuo. 2.05 g of the desired title compound are obtained in the form of a white solid having a melting point of 171-172° C.

Example P53

3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfinylethyl)-[1H]-pyridin-2-one

1.18 g o 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-1-methanesulfanylethyl)-[1H]-pyridin-2-one are introduced into 7 ml of glacial acetic acid. After the addition of 0.27 g of hydrogen peroxide/urea adduct, the mixture is stirred overnight at 22° C. The next day, the reaction mixture is taken up in ethyl acetate and washed in succession with dilute sodium hydroxide solution, dilute hydrochloric acid and brine. After drying over sodium sulfate, the mixture is filtered and concentrated to dryness in vacuo. The residue (1.12 g of a yellow solid) is stirred with 10 ml of diethyl ether, and then filtered and washed with n-hexane. 1.05 g of the desired compound are obtained in the form of a white solid having a melting point of 143-145° C.

Example P54

1-Benzyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridine-2-thione

0.50 g of 1-benzyl-3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-[1H]-pyridin-2-one is introduced into 5 ml of toluene, 0.63 g of Lawesson's reagent is added and the resulting yellow suspension is stirred overnight at 120° C. The next day, the mixture is cooled to 22° C., diluted with methylene chloride and, after the addition of 3 g of silica gel, concentrated to dryness in vacuo. The silica gel is applied to a flash chromatography column and eluted first with toluene/ethyl acetate 30/1 (v/v) and then with n-hexane/ethyl acetate 2/1 (v/v). 0.32 g of the desired title compound is obtained in the form of a yellow solid having a melting point of 135-138° C.

The R_(f) value of the starting material on silica gel 60 F₂₅₄ (eluant: toluenelethyl acetate 30/1 (v/v)) is 0.02 and the R_(f) value of the title compound is 0.18.

Example P55

3-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoro-2-oxo-[2H]-pyridin-1-yl)-propionaldehyde

0.40 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-1-(2-[1.3]-dioxolan-2-ylethyl)-5-fluoro-[1H]-pyridin-2-one is stirred overnight at 22° C. in a mixture of 6 ml of 2N hydrochloric acid and 6 ml of diethyl ether. The next day, the same amount of the mixture together with 2 ml of tetrahydrofuran are added and the mixture is again stirred overnight. The mixture is subsequently diluted with diethyl ether and washed three times with brine, dried over sodium sulfate, filtered and concentrated to dryness in vacuo. 0.23 g of the desired compound (crude) is obtained in the form of a yellow oil.

¹H-NMR (CDCl₃): 9.73 ppm (s, 1H); 7.61 ppm (d, 1H); 6.73 ppm (t, 1H); 4.15 ppm (broad signal, 2H); 3.85 ppm (s, 3H); 2.98 ppm (t, 2H).

Example P56

2-(3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-yloxy)-acetamide

20.0 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ol (Example P27) are placed together with 18.9 g of potassium carbonate and 6.4 g of chloroacetamide at 22° C. and the mixture is stirred overnight at 50° C. The next day, the mixture is cooled to 22° C. and then introduced into 2 liters of ice-water. After subsequently stirring for 10 minutes at 22° C., the resulting slurry is filtered. The filtration residue is washed with cold water and then dried in vacuo at 60° C. 20.2 g of the desired title compound are obtained in the form of a white solid having a melting point of 178-180° C.

Example P57

3-Chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-ylamine

7.1 g of potassium carbonate are introduced into 200 ml of dry N-methylpyrrolidone (NMP) and the mixture is heated to a temperature of 150° C. With stirring, 19.6 g of 2-(3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-5-fluoropyridin-2-yloxy)-acetamide (Example P56) are introduced in portions in the course of 2 hours and then the mixture is stirred for 10 hours at 150° C., subsequently cooled to 22° C. and partitioned between diethyl ether and water. After extraction by shaking, and separation of the phases, the ethereal phase is washed with brine, dried over sodium sulfate, filtered and concentrated together with twice the amount of silica gel. The silica gel is applied to a flash chromatography column and then elution is carried out with a n-hexane/ethyl acetate 111 (v/v) mixture. 9.3 g of the desired title compound having a melting point of 100-101° C. are obtained.

The R_(f) value of the starting material on silica gel 60 F₂₅₄ (eluant: n-hexane/ethyl acetate 1/1 (v/v)) is 0.14 and the R_(f) value of the target compound is 0.43.

Example P58

8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoro-imidazo[1,2-a]pyridine-2-carboxylic Acid Ethyl Ester

1.96 g of 3-chloro-6-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-S-fluoropyridin-2-ylamine (Example P57) are placed together with 1.25 ml of bromopyruvic acid ethyl ester (90%) in 20 ml of absolute ethanol. The mixture is stirred for 6 hours at 90° C. and then cooled to 22° C. and concentrated to dryness in vacuo. The residue is crystallised by the addition of diethyl ether and stirred, and n-hexane is added until precipitation is complete. The crystal fraction is filtered off, washed with n-hexane and dried in vacuo. 2.52 g of a yellowish-brown solid are obtained, which is dissolved in ethyl acetate and washed with dilute sodium hydrogen carbonate solution and then with brine. The organic phase is dried over sodium sulfate and then filtered and concentrated to dryness in vacuo. The residue obtained is digested in n-hexane, filtered, washed and dried. 1.88 g of the title compound are obtained in the form of a beige solid having a melting point of 140-143° C.

Example P59

8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6fluoro-imidazo[1,2-a]pyridine-2-carboxylic Acid

0.51 g of 8-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoro-imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (Example P58) is dissolved in 3 ml of dimethyl sulfoxide and, with cooling in an ice-bath, 0.63 ml of a 2N aqueous sodium hydroxide solution is added. The mixture is then stirred for 1 hour at 22° C. Because the TLC analysis of a worked-up sample indicates that starting material is still present, a further 0.1 ml of 2N sodium hydroxide solution is added. After subsequently stirring for 30 minutes, the mixture is rendered strongly acidic with dilute hydrochloric acid, the resulting slurry is filtered, and the filtration residue is subsequently washed with cold water and dried in vacuo at 50° C. 0.35 g of the desired title compound is obtained in the form of a white solid (crude product).

Example P60

8-Chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoro-imidazo[1,2-a]pyridin-2-yl)methanol

0.56 g of 8-chloro-5-(4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazol-3-yl)-6-fluoro- imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (Example P58) is introduced at 22° C. into 5 ml of diethyl ether and then treated with a total of 0.18 g of lithium aluminium hydride in portions with stirring. The resulting reddish-brown suspension is subsequently stirred for 1 hour and then first an excess of ethyl acetate and then dilute hydrochloric acid are added dropwise. The separated organic phase is washed with brine, filtered and concentrated to dryness in vacuo. 0.14 g of a yellowish-brown oil is obtained, which is purified over silica gel using ethyl acetate as eluant. 0.40 g of the desired compound is obtained in the form of a beige solid having a melting point of 152-153° C.

The preferred compounds listed in the following Tables can also be prepared in an analogous manner, and according to methods such as are illustrated in the general Reaction Schemes 1-3 and in the references quoted.

Table 1:

A preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁.

Table 2:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂.

Table 3:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃.

Table 4:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₄.

Table 5:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₅.

Table 6:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₆.

Table 7:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₇.

Table 8:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₈.

Table 9:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₉.

Table 10:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₀.

Table 11:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₁.

Table 12:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₂.

Table 13:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₃.

Table 14:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₄.

Table 15:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₅.

Table 16:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₆.

Table 17:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₇.

Table 18:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₈.

Table 19:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₁₉.

Table 20:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂₀.

Table 21:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂₁.

Table 22:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂₂.

Table 23:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂₃.

Table 24:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂₄.

Table 25:

Another preferred group of compounds of formula I corresponds to the general

in which the sets of correlated substituents R₁₁, X₁ and R₁3 are given in Table A, thus disclosing 654 specific compounds of formula I₂₅.

Table 26:

Another preferred group of compounds of formula I corresponds to the general

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table Ax thus disclosing 654 specific compounds of formula I₂₆.

Table 27:

Another preferred group of compounds of formula i corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂₇.

Table 28:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂₈.

Table 29:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₂₉.

Table 30:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃₀.

Table 31:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃₁.

Table 32:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃₂.

Table 33:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃₃.

Table 34:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃₄.

Table 35: Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃₅.

Table 36: Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃₆.

Table 37:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, X₁ and R₁₃ are given in Table A, thus disclosing 654 specific compounds of formula I₃₇.

TABLE A Compd. No. R₁₁ X₁ R₁₃ .001 H O CH₃ .002 F O CH₃ .003 Cl O CH₃ .004 F O CH₂CH₃ .005 Cl O CH₂CH₃ .006 H O CH₂CH₃ .007 F O CH₂CH₂CH₃ .008 Cl O CH₂CH₂CH₃ .009 H O CH₂CH₂CH₃ .010 F O CH₂CH₂CH₂CH₃ .011 Cl O CH₂CH₂CH₂CH₃ .012 F O CH₂CH₂CH₂CH₂CH₃ .013 Cl O CH₂CH₂CH₂CH₂CH₃ .014 F O CH₂CH₂CH₂CH₂CH₂CH₃ .015 F O CH₂CH₂CH(CH₃)₂ .016 Cl O CH₂CH₂CH(CH₃)₂ .017 H O CH₂CH₂CH(CH₃)₂ .018 F O CH₂CH(CH₃)CH₂CH₃ .019 Cl O CH₂CH(CH₃)CH₂CH₃ .020 H O CH₂CH(CH₃)CH₂CH₃ .021 F O CH₂CH(CH₃)CH₂CH₂CH₃ .022 F O CH₂CH₂CH(CH₃)CH₂CH₃ .023 F O CH₂CH₂CH₂CH(CH₃)₂ .024 F O CH(CH₃)CH₂CH₂CH₂CH₃ .025 Cl O CH(CH₃)CH₂CH₂CH₂CH₃ .026 H O CH(CH₃)CH₂CH₂CH₂CH₃ .027 F O CH₂C(CH₃)₃ .028 Cl O CH₂C(CH₃)₃ .029 H O CH₂CH(CH₃)₂ .030 Cl O CH₂CH(CH₃)₂ .031 F O CH₂CH(CH₃)₂ .032 F O CH₂C(CH₃)₂CH₂CH₃ .033 Cl O CH₂C(CH₃)₂CH₂CH₃ .034 H O CH₂C(CH₃)₂CH₂CH₃ .035 F O CH₂CH₂C(CH₃)₃ .036 Cl O CH₂CH₂C(CH₃)₃ .037 F O CH₂CH₂CHCH₂ .038 Cl O CH₂CH₂CHCH₂ .039 H O CH₂CH₂CHCH₂ .040 F O CH₂CH₂CH₂CHCH₂ .041 Cl O CH₂CH₂CH₂CHCH₂ .042 H O CH₂CH₂CH₂CHCH₂ .043 F O CH₂CH₂CH₂CH₃ .044 F O CH(CH₃)₂ .045 F O CH₂CF₃ .046 Cl O CH₂CF₃ .047 H O CH₂CF₃ .048 F O CH₂CHF₂ .049 Cl O CH₂CHF₂ .050 F O CH₂CH₂CF₃ .051 Cl O CH₂CH₂CF₃ .052 F O CH₂CCl₃ .053 F O CH₂CH₂CF₃ .054 Cl O CH₂CH₂CF₃ .055 F O CH₂CH₂CHF₂ .056 Cl O CH₂CH₂CHF₂ .057 H O CH₂CH₂CHF₂ .058 F O CH₂CH₂CH(OH)CH₃ .059 F O CH₂CH(OH)CH₂CH₃ .060 Cl O CH₂CH(OH)CH₂CH₃ .061 F Cl CH₂CH(OH)CH₃ .062 H O CH₂CH₂CHClCH₃ .063 Cl O CH₂CH₂CHClCH₃ .064 F O CH₂CH₂CHClCH₃ .065 F O CH₂CH₂CHFCH₃ .066 F O CH₂CHFCH₂CH₃ .067 Cl O CH₂CHFCH₂CH₃ .068 H O CH₂CHFCH₂CH₃ .069 F O CH₂CHClCH₂CH₃ .070 F O CH₂CH₂F .071 Cl O CH₂CH₂F .072 F O CH₂CH₂Cl .073 F O CH₂CH₂Br .074 Cl O CH₂CH₂Cl .075 H O CH₂CH₂Cl .076 F O CH₂CHF₂ .077 F O CH₂CHBr₂ .078 H O CH₂CHCH₂ .079 Cl O CH₂CHCH₂ .080 F O CH₂CHCH₂ .081 F O CH₂CH(CH₃)CH₂ .082 F O CH₂CHCH(CH₃) .083 F O CH₂CHCH(Cl) (E-form) .084 Cl O CH₂CHCH(Cl) (E-form) .085 H O CH₂CHCH(Cl) (E-form) .086 F O CH₂CHCH(Cl) (Z-form) .087 Cl O CH₂CHCH(Cl) (Z-form) .088 H O CH₂CH₂OH .089 Cl O CH₂CH₂OH .090 F O CH₂CH₂OH .091 F O CH₂CH₂CH₂OH .092 Cl O CH₂CH₂CH₂OH .093 F O CH₂CH(OH)CH₃ .094 Cl O CH₂CH(OH)CH₃ .095 F O CH₂CHCHCl .096 Cl O CH₂CHCHCl .097 H O CH₂CHCHCl .098 H O CH₂CCH .099 Cl O CH₂CCH .100 F O CH₂CCH .101 F O CH₂CH(CH₃)CCH .102 Cl O CH₂CH₂CCH .103 F O CH₂CH₂CCH .104 Cl O CH₂CH₂C₆H₅ .105 F O CH₂CH₂C₆H₅ .106 F O CH₂CH₂CH₂C₆H₅ .107 F O CH₂CH₂CH(CH₃)C₆H₅ .108 F O CH₂CH₂CH₂CH₂(p-F—C₆H₄) .109 H O CH₂C₆H₅ .110 Cl O CH₂C₆H₅ .111 F O CH₂C₆H₅ .112 F O CH₂(o-F—C₆H₄) .113 H O CH₂(p-Cl—C₆H₄) .114 F O CH₂(m-CF₃—C₆H₄) .115 F O CH₂(3,4-di-Cl—C₆H₃) .116 F O CH₂(3,5-di-CH₃—C₆H₃) .117 F O CH₂CH₂(2,6-di-F—C₆H₃) .118 Cl O CH₂CH₂(2,6-di-F—C₆H₃) .119 H O CH₂CH₂(2,6-di-F—C₆H₃) .120 F O CH₂CH₂CH₂(4-F—C₆H₄) .121 Cl O CH₂CH₂CH₂(4-F—C₆H₄) .122 F O CH₂CH₂CH(CH₃)(4-CH₃—C₆H₄) .123 Cl O CH₂CH₂CH(CH₃)(4-CH₃—C₆H₄) .124 H O CH₂CN .125 Cl O CH₂CN .126 F O CH₂CN .127 F O CH₂CHFCN .128 F O cyclopropyl .129 F O cyclopentyl .130 F O CH₂-cyclopentyl .131 F O CH₂-cyclopropyl .132 F O CH₂CH₂Cl .133 F O CH₂CHCl₂ .134 H O CH₂OCH₃ .135 Cl O CH₂OCH₃ .136 F O CH₂OCH₃ .137 F O CH₂CH₂OCH₃ .138 Cl O CH₂CH₂OCH₃ .139 H O CH₂CH₂OCH₃ .140 F O CH₂CH₂OCH₂CH₃ .141 F O CH₂CH(CH₃)OCH₃ .142 H O CH₂CH₂OCH₂CH₂OCH₃ .143 Cl O CH₂CH₂OCH₂CH₂OCH₃ .144 F O CH₂CH₂OCH₂CH₂OCH₃ .145 H O CH₂SCH₃ .146 Cl O CH₂SCH₃ .147 F O CH₂SCH₃ .148 H O CH₂S(O)CH₃ .149 Cl O CH₂S(O)CH₃ .150 F O CH₂S(O)CH₃ .151 H O CH₂S(O)₂CH₃ .152 Cl O CH₂S(O)₂CH₃ .153 F O CH₂S(O)₂CH₃ .154 F O CH₂SCH₂CH₃ .155 F O CH₂CH₂SCH₃ .156 F O CH₂CH₂SCH₂CH₃ .157 Cl O CH₂CH₂SCH₂CH₃ .158 H O CH₂CH₂SCH₂CH₃ .159 Cl O CH₂CH₂SCH₃ .160 H O CH₂CH₂SCH₃ .161 F O CH₂CH₂S(O)CH₃ .162 F O CH₂CH₂S(O)₂CH₃ .163 Cl O CH₂CH₂S(O)CH₃ .164 Cl O CH₂CH₂S(O)₂CH₃ .165 F O CH₂CH₂S(O)CH₂CH₃ .166 Cl O CH₂CH₂S(O)CH₂CH₃ .167 H O CH₂CH₂S(O)CH₂CH₃ .168 F O CH₂CH₂S(O)₂CH₂CH₃ .169 Cl O CH₂CH₂S(O)₂CH₂CH₃ .170 H O CH₂CH₂S(O)₂CH₂CH₃ .171 F O CH₂CH₂CH₂SCH₃ .172 F O CH₂CH₂CH₂S(O)CH₃ .173 F O CH₂CH₂CH₂S(O)₂CH₃ .174 F O CH₂CH(CH₃)SCH₃ .175 H O CH₂COOH .176 Cl O CH₂COOH .177 F O CH₂COOH .178 F O CH₂COOCH₃ .179 H O CH₂COOCH₂CH₃ .180 Cl O CH₂COOCH₂CH₃ .181 F O CH₂COOCH₂CH₃ .182 F O CH₂COOCH(CH₃)₂ .183 Cl O CH₂COOCH(CH₃)₂ .184 H O CH₂COOCH(CH₃)₂ .185 F O CH₂COOCH(CH₂CH₃)₂ .186 Cl O CH₂CCOCH(CH₃)CH₂CH₃ .187 F O CH₂COOCH₂CH₂CH₃ .188 F O CH₂COOCH₂CH₂CH₂CH₃ .189 F O CH₂COOCH₂CH(CH₃)₂ .190 F O CH₂COOC(CH₃)₃ .191 F O CH₂COOCH₂CHCH₂ .192 F O CH₂COOCH₂CCH .193 Cl O CH₂COOCH₂CCH .194 H O CH₂COOCH₂CCH .195 F O CH₂COOCH₂C₆H₅ .196 F O CH₂COOCH₂(o-F—C₆H₄) .197 F O CH₂COOCH₂(p-Cl—C₆H₄) .198 F O CH₂COOCH₂(m-CH₃—C₆H₄) .199 F O CH₂COOCH₂(2,4-di-CH₃—C₆H₃) .200 Cl O CH₂COOCH₂(2,4-di-CH₃—C₆H₃) .201 F O CH₂CH₂COOCH₂(3,4-di-Cl—C₆H₃) .202 F O CH₂CH₂CH₂COOH .203 Cl O CH₂CH₂CH₂COOH .204 F O CH₂CH₂CH₂CCOCH₃ .205 F O CH₂CH₂CH₂COOCH₂CH₃ .206 Cl O CH₂CH₂CH₂COOCH₂CH₃ .207 F O CH₂CH₂CH₂CH₂COOH .208 F O CH₂CH₂CH₂CH₂COOCH₃ .209 Cl O CH₂CH₂CH₂CH₂COOCH₃ .210 H O CH₂CH₂CH₂CH₂COOCH₃ .211 H O CH₂CHO .212 Cl O CH₂CHO .213 F O CH₂CHO .214 H O CH₂C(O)CH₃ .215 Cl O CH₂C(O)CH₃ .216 F O CH₂C(O)CH₃ .217 F O CH₂C(O)SCH₃ .218 Cl O CH₂C(O)SCH₃ .219 F O CH₂C(O)SCH₂CH₂CH₃ .220 Cl O CH₂C(O)SCH₂CH₂CH₃ .221 F O CH₂C(O)SCH₂CHCH₂ .222 Cl O CH₂C(O)SCH₂CHCH₂ .223 F O CH₂COSCH₂CH₃ .224 H O CH₂COSCH(CH₃)₂ .225 Cl O CH₂COSCH(CH₃)₂ .226 F O CH₂COSCH(CH₃)₂ .227 F O CH₂COSCH₂C₆H₅ .228 Cl O CH₂COSCH₂C₆H₅ .229 H O CH₂COSCH₂C₆H₅ .230 F O CH₂CONH₂ .231 F O CH₂CONH(CH₃) .232 F O CH₂CON(CH₃)₂ .233 Cl O CH₂CON(CH₃)₂ .234 F O CH₂CON(CH₂CH₃)₂ .235 Cl O CH₂CON(CH₂CH₃)₂ .236 H O CH₂CON(CH₂CH₃)₂ .237 F O CH₂CON(CH₂CH₃)(CH₃) .238 F O CH₂CON(CH₂CH₂CH₃)₂ .239 Cl O CH₂CON(CH₂CH₂CH₃)₂ .240 H O CH₂CONH(CH₂CH₂CH₃) .241 F O CH₂CONH(CH₂CH₂CH₃) .242 H O CH₂CONHCH₂CHCH₂ .243 Cl O CH₂CONHCH₂CHCH₂ .244 F O CH₂CONHCH₂CHCH₂ .245 H O CH₂CONHCH₂CCH .246 Cl O CH₂CONHCH₂CCH .247 F O CH₂CONHCH₂CCH .248 F O CH₂CONHC₆H₅ .249 Cl O CH₂CONHC₆H₅ .250 F O CH₂CONH(3,4-di-Cl—C₆H₃) .251 F O CH₂CON(CH₃)(C₆H₅) .252 Cl O CH₂CON(CH₃)(C₆H₅) .253 F O CH₂CONH(o-F—C₆H₄) .254 F O CH₂CONHCH₂(C₆H₆) .255 Cl O CH₂CONHCH₂(C₆H₅) .256 H O CH₂CONHCH₂(C₆H₅) .257 F O CH₂CON(CH₃)CH₂(C₆H₅) .258 F O CH₂CONH(3,4-di-Cl—C₆H₃) .259 Cl O CH₂CONH(3,4-di-Cl—C₆H₃) .260 F O CH₂CONHCH₂(4-Cl—C₅H₄) .261 Cl O CH₂CONHCH₂(4-Cl—C₆H₄) .262 F O CH₂CON(CH₃)CH₂(4-Cl—C₆H₄) .263 F O CH₂CON(CH₂CH₃)CH₂(4-Cl—C₆H₄) .264 Cl O CH₂CON(CH₂CH₃)CH₂(4-Cl—C₆H₄) .265 F O CH₂CON(CH₂CHCH₂)CH₂(4-Cl—C₆H₄) .266 Cl O CH₂CON(CH₂CHCH₂)CH₂(4-Cl—C₆H₄) .267 H O CH₂CH₂COOH .268 Cl O CH₂CH₂COOH .269 F O CH₂CH₂COOH .270 F O CH₂CH₂COOCH₂CH₃ .271 Cl O CH₂CH₂COOCH₂CH₃ .272 H O CH₂CH₂COOCH₂CH₃ .273 F O CH₂CH₂COOCH₂CHCH₂ .274 Cl O CH₂CH₂COOCH₂CHCH₂ .275 F O CH₂CH₂COOCH₂(C₆H₅) .276 F O CH₂CH₂COOCH(CH₃)₂ .277 Cl O CH₂CH₂COOCH(CH₃)₂ .278 H O CH₂CH₂CN .279 Cl O CH₂CH₂CN .280 F O CH₂CH₂CN .281 F O CH₂CH(CH₃)CN .282 Cl O CH₂CH(CH₃)CN .283 H O CH₂CH(CH₃)CN .284 F O CH₂CH(Cl)CN .285 Cl O CH₂CH(Cl)CN .286 F O CH₂CH₂CH₂CN .287 Cl O CH₂CH₂CH₂CN .288 F O CH₂CH₂CH(CH₃)CN .289 F O CH₂CH(CH₃)CH₂CN .290 Cl O CH₂CH(CH₃)CHO .291 Cl O CH(CH₃)CH₂CN .292 H O CH₂CH₂CHO .293 Cl O CH₂CH₂CHO .294 F O CH₂CH₂CHO .295 F O CH₂CH(Cl)CHO .296 Cl O CH₂CH(Cl)CHO .297 F O CH₂CH(CH₃)CHO .298 Cl O CH₂CH(CH₃)CHO .299 H O CH₂CH(CH₃)CHO .300 F O CH₂CH₂C(O)CH₃ .301 Cl O CH₂CH₂C(O)CH₃ .302 F O CH₂COCH₂CH₃ .303 Cl O CH₂COCH₂CH₃ .304 H O CH₂COCH₂CH₃ .305 F O CH₂COCH₂CH₂CH₃ .306 F O CH₂CH₂COCH₂CH₃ .307 F O CH₂CH₂COCH₂CH₃ .308 F O CH₂CH(CH₃)COOH .309 Cl O CH₂CH(CH₃)COOH .310 H O CH₂CH(CH₃)COOH .311 F O CH₂CH(CH₃)COOCH₃ .312 F O CH₂CH(CH₃)COOCH₂CH₃ .313 Cl O CH₂CH(CH₃)COOCH₂CH₃ .314 F O CH₂CH₂CH₂COOH .315 Cl O CH₂CH₂CH₂COOH .316 Cl O CH₂CH₂CH₂COOCH₃ .317 F O CH₂CH₂CH₂COOCH₃ .318 F O CH₂CH₂CH₂COSCH₂CH₃ .319 F O CH₂CH₂CH₂CONHCH₂CCH .320 F O CH₂CH₂CH₂CON(CH₃)(CH₂CCH) .321 F O CH₂CH₂CH₂CON(CH₃)₂ .322 F O CH₂CH₂CH(CH₃)COOCH₂CH₃ .323 H O CH₂CH(OH)COOH .324 Cl O CH₂CH(OH)COOH .325 F O CH₂CH(OH)COOH .326 H O CH₂CH(Cl)COOH .327 Cl O CH₂CH(Cl)COOH .328 F O CH₂CH(Cl)COOH .329 Cl O CH₂CH(Cl)COOCH₂CH₃ .330 F O CH₂CH(Cl)COOCH₂CH₃ .331 F O CH₂CH(Cl)COOCH₂(4-Cl—C₆H₄) .332 F O CH₂CH(Cl)COOCH₂CHCH₂ .333 Cl O CH₂CH(Cl)COOCH₂CHCH₂ .334 F O CH₂CH(Cl)COOC(CH₃)₃ .335 Cl O CH₂CH(Cl)COOC(CH₃)₃ .336 F O CH₂CH(Cl)COOCH₂CH₂CH₃ .337 F O CH₂C(CH₃)(Cl)COOH .338 Cl O CH₂C(CH₃)(Cl)COOH .339 H O CH₂C(CH₃)(Cl)COOH .340 F O CH₂CH(Cl)COOCH₂CHCH₂ .341 Cl O CH₂CH(Cl)COOCH₂CHCH₂ .342 H O CH₂CH(Cl)COOCH₂CHCH₂ .343 F O CH₂CH(Cl)COOCH₂CCH .344 F O CH₂CH(Cl)COOCH₂C₆H₅ .345 F O CH₂CH(Br)COOH .346 Cl O CH₂CH(Br)COOH .347 H O CH₂CH(Br)COOH .348 F O CH₂CH(Br)COOCH₃ .349 Cl O CH₂CH(Br)COOCH₃ .350 F O CH₂CH(Br)COOCH₂CH₃ .351 F O CH₂CH(Br)COOCH₂CHCH₂ .352 Cl O CH₂CH(Br)COOCH₂CHCH₂ .353 F O CH₂CH(Br)COOCH₂CCH .354 Cl O CH₂CH(Br)COOCH₂CCH .355 F O CH₂CHBrCOOC(CH₃)₃ .356 Cl O CH₂CHBrCOOC(CH₃)₃ .357 F O CH₂CH(Cl)C(O)SCH(CH₃)₂ .358 F O CH₂CH(Cl)C(O)NH₂ .359 Cl O CH₂CH(Cl)C(O)NH₂ .360 F O CH₂CH(Cl)C(O)NH(CH₂CCH) .361 Cl O CH₂CH(Cl)C(O)NH(CH₂CCH) .362 F O CH₂CH(Cl)C(O)NH(CH₂CHCH₂) .363 F O CH₂CH(Cl)C(O)N(CH₂CH₃)(CH₂CHCH₂) .364 Cl O CH₂CH(Cl)C(O)N(CH₂CH₃)(CH₂CHCH₂) .365 F O CH₂CH(CH₃)C(O)N(CH₃)(CH₂CHCH₂) .366 F O CH₂COOCH₂CH₂Cl .367 F O CH₂COOCH₂CF₃ .368 Cl O CH₂COOCH₂CF₃ .369 H O CH₂COOCH₂CF₃ .370 F O CH₂COOCH₂CH₂F .371 Cl O CH₂COOCH₂CH₂F .372 F O CH₂COOCH₂CH₂Cl .373 Cl O CH₂COOCH₂CH₂Cl .374 F O CH₂COOCH₂CH₂CH₂Cl .375 F O CH₂COOCH₂CH(Cl)CH₃ .376 Cl O CH₂COOCH₂CH(Cl)CH₃ .377 F C CH₂COOCH₂CH(F)CH₃ .378 Cl O CH₂COOCH₂CH(F)CH₃ .379 H O

.380 H O

.381 Cl O

.382 Cl O

.383 F O

.384 F O

.385 F O S(O)₂CH₃ .386 F O S(O)₂CH₂CH₃ .387 Cl O S(O)₂CF₃ .388 Cl O S(O)₂CH₂CH₃ .389 F O S(O)₂CH(CH₃)₂ .390 H O C(O)CH₃ .391 Cl O C(O)CH₃ .392 F O C(O)CH₃ .393 F O C(O)CF₃ .394 F O C(O)CH₂CH₃ .395 H O OH .396 Cl O OH .397 F O OH .398 H O OCH₃ .399 Cl O OCH₃ .400 F O OCH₃ .401 H O OCH₂CH₃ .402 Cl O OCH₂CH₃ .403 F O OCH₂CH₃ .404 F O OCH₂CH(CH₃)₂ .405 F O OCH₂C(CH₃)₃ .406 F O OCF₃ .407 F O OCHF₂ .408 F O OCH₂CHCH₂ .409 F O OCH₂C(CH₃)CH₂ .410 F O OCH₂CHCHCl .411 H O OCH₂OCH₃ .412 Cl O OCH₂OCH₃ .413 F O OCH₂OCH₃ .414 H O OCH₂SCH₃ .415 Cl O OCH₂SCH₃ .416 F O OCH₂SCH₃ .417 F O OCH₂CCH .418 H O OCH₂COOH .419 Cl O OCH₂COOH .420 F O OCH₂COOH .421 F O OCH₂COOCH₃ .422 F O OCH₂COOCH₂CH₃ .423 F O OCH₂COOCH(CH₃)₂ .424 H O OCH(CH₃)COOH .425 Cl O OCH(CH₃)COOH .426 F O OCH(CH₃)COOH .427 F O OCH(CH₃)COOCH₂CH₃ .428 F O OCH(CH₃)COOCH₂CCH .429 F O OCH(CH₃)COOCH₂CHCH₂ .430 F O OCH₂COSCH₂CH₃ .431 H O OCH₂COSCH(CH₃)₂ .432 Cl O OCH₂COSCH(CH₃)₂ .433 F O OCH₂COSCH(CH₃)₂ .434 F O OCH₂COSCH₂C₆H₅ .435 F O OCH₂CONH₂ .436 F O OCH₂CON(CH₃)₂ .437 H O OCH₂CONHCH₂CCH .438 Cl O OCH₂CONHCH₂CCH .439 F O OCH₂CONHCH₂CCH .440 F O OCH₂C₆H₅ .441 F O OCH₂(p-CH₃O—C₆H₄) .442 F O OCH₂(o-F—C₆H₄) .443 Cl O OCH₂(m-CF₃—C₆H₄) .444 F O OCH₂CH₂C₆H₅ .445 H O OCH₂CN .446 H O OCH₂CH₂Cl .447 Cl O OCH₂CN .448 Cl O OCH₂CH₂Cl .449 F O OCH₂CN .450 F O OCH₂CH₂Cl .451 F O OCH₂CH₂CF₃ .452 H O OCH₂CH₂OH .453 Cl O OCH₂CH₂OH .454 F O OCH₂CH₂OH .455 H O OCH₂CH₂CN .456 Cl O OCH₂CH₂CN .457 F O OCH₂CH₂CN .458 F O OCH₂CH(OH)(C₆H₅) .459 F O OCH₂CH(OH)(CH₃) .460 Cl O OCH₂CH(OCH₃)(CH₃) .461 F O OCH₂CH(OCH₃)(CH₃) .462 H O OC(O)CH₃ .463 Cl O OC(O)CH₃ .464 F O OC(O)CH₃ .465 H S CH₃ .466 Cl S CH₃ .467 F S CH₃ .468 H S CH₂CH₃ .469 Cl S CH₂CH₃ .470 F S CH₂CH₃ .471 F S CH₂CH₂CH₃ .472 F S CH₂CH(CH₃)₂ .473 F S CH₂CH₂CF₃ .474 F S CH(CH₃)₂ .475 F S CH₂CH(CH₃)₂ .476 F S CH₂CH(Cl)CH₃ .477 F S CH₂CH₂CH(Cl)CH₃ .478 F S CH₂CH₂CH(OH)CH₃ .479 H S CH₂CHCH₂ .480 Cl S CH₂CHCH₂ .481 F S CH₂CHCH₂ .482 F S CH₂C(CH₃)CH₂ .483 H S CH₂CCH .484 Cl S CH₂CCH .485 F S CH₂CCH .486 F S CH₂CH₂CCH .487 F S CH(CH₃)CCH .488 H S CH₂CH₂OH .489 Cl S CH₂CH₂OH .490 F S CH₂CH₂OH .491 F S CH₂CH(OH)CH₃ .492 H S CH₂C₆H₅ .493 Cl S CH₂C₆H₅ .494 F S CH₂C₆H₅ .495 Cl S CH₂(o-F—C₆H₄) .496 F S CH₂(o-F—C₆H₅) .497 F S CH₂(m-CF₃—C₆H₅) .498 F S CH₂(p-CH₃—C₆H₄) .499 F S CH₂(2,4-di-F—C₆H₃) .500 F S CH₂CH₂CH(CH₃)C₆H₅ .501 F S CH₂CH₂CH₂CH₂(p-F—C₆H₄) .502 Cl S CH₂CN .503 F S CH₂CN .504 F S cyclopropyl .505 Cl S CH₂-cyclopropyl .506 F S CH₂-cyclopropyl .507 F S CH₂Cl .508 H S CH₂OCH₃ .509 Cl S CH₂OCH₃ .510 F S CH₂OCH₃ .511 F S CH₂OCH₂CHCH₂ .512 F S CH₂CH₂OCH₃ .513 F S CH₂CH(OCH₃)CH₃ .514 F S CH₂CH(OCH₂CCH)CH₃ .515 H S CH₂CH₂OCH₂CH₂OCH₃ .516 Cl S CH₂CH₂OCH₂CH₂OCH₃ .517 F S CH₂CH₂OCH₂CH₂OCH₃ .518 H S CH₂SCH₃ .519 Cl S CH₂SCH₃ .520 F S CH₂SCH₃ .521 F S CH₂SCH₂CHCH₂ .522 F S CH₂SCH₂CCH .523 F S CH₂CH₂SCH₃ .524 F S CH₂CH₂S(O)CH₃ .525 F S CH₂CH₂S(O)₂CH₃ .526 H S CH₂COOH .527 Cl S CH₂COOH .528 F S CH₂COOH .529 F S CH₂COOCH₃ .530 F S CH₂COOCH₂CH₃ .531 F S CH₂COOC(CH₃)₃ .532 F S CH₂COOCH₂C₆H₅ .533 F S CH₂COOCH₂(p-Cl—C₆H₄) .534 F S CH₂C(O)SCH₃ .535 H S CH₂C(O)SCH(CH₃)₂ .536 Cl S CH₂C(O)SCH(CH₃)₂ .537 F S CH₂C(O)SCH(CH₃)₂ .538 F S CH₂C(O)SCH₂C₆H₅ .539 F S CH₂C(O)NH₂ .540 F S CH₂C(O)NH(CH₃) .541 Cl S CH₂C(O)NH(CH₂CCH) .542 F S CH₂C(O)NH(CH₂CCH) .543 F S CH₂C(O)N(CH₂CH₃)₂ .544 H S CH₂CHO .545 Cl S CH₂CHO .546 F S CH₂CHO .547 F S CH₂C(O)CH₃ .548 H S CH₂CH₂COOH .549 Cl S CH₂CH₂COOH .550 F S CH₂CH₂COOH .551 H S CH₂CH₂CN .552 Cl S CH₂CH₂CN .553 F S CH₂CH₂CN .554 F S CH₂CH₂COOCH₃ .555 F S CH₂CH₂COOCH₂C₆H₅ .556 Cl S CH₂CH₂C(O)SCH₂CH₃ .557 F S CH₂CH₂C(O)SCH₂CH₃ .558 H S CH₂CH(OH)COOH .559 Cl S CH₂CH(OH)COOH .560 F S CH₂CH(OH)COOH .561 H S CH₂CH(Cl)COOH .562 Cl S CH₂CH(Cl)COOH .563 F S CH₂CH(Cl)COOH .564 Cl S CH₂CH(Cl)COOCH₂CH₃ .565 F S CH₂CH(Cl)COOCH₂CH₃ .566 F S CH₂CH(Cl)COOH .567 F S CH₂C(CH₃)(Cl)COOH .568 F S CH₂CH(Cl)COOCH₂CHCH₂ .569 Cl S CH₂CH(Cl)COOCH₂CCH .570 F S CH₂CH(Cl)COOCH₂CCH .571 F S CH₂CH(Cl)COOCH₂C₆H₅ .572 Cl S CH₂CH(Br)COOH .573 F S CH₂CH(Br)COOH .574 Cl S CH₂CH(Cl)C(O)SCH(CH₃)₂ .575 F S CH₂CH(Cl)C(O)SCH(CH₃)₂ .576 F S CH₂CH(Cl)C(C)NH(CH₂CCH) .577 F S CH₂CH(CH₃)C(O)N(CH₃)(CH₂CHCH₂) .578 F S CH₂CH₂C(O)NH(CH₂CCH) .579 H S

.580 Cl S

.581 F S

.582 H S

.583 Cl S

.584 F S

.585 H S OH .586 Cl S OH .587 F S OH .588 H S OCH₃ .589 Cl S OCH₃ .590 F S OCH₃ .591 F S OCH₂CH₃ .592 Cl S OCH₂CH(CH₃)₂ .593 F S OCH₂CH(CH₃)₂ .594 F S OCH(CH₃)₂ .595 F S OCF₃ .596 H S OCH₂OCH₃ .597 Cl S OCH₂OCH₃ .598 F S OCH₂OCH₃ .599 H S OCH₂SCH₃ .600 Cl S OCH₂SCH₃ .601 F S OCH₂SCH₃ .602 Cl S OCH₂CHCH₂ .603 F S OCH₂CHCH₂ .604 H S OCH₂CCH .605 Cl S OCH₂CCH .606 F S OCH₂CCH .607 F S OCH(CH₃)CHCH₂ .608 F S OCH(CH₃)CCH .609 F S OCH₂CH₂Cl .610 F S OCH₂CH₂CF₃ .611 F S OCH₂CHCH(Cl) .612 H S OCH₂CHO .613 H S OCH₂CHO .614 H S OCH₂CHO .615 H S OCH₂COOH .616 Cl S OCH₂COOH .617 F S OCH₂COOH .618 H S OCH₂COOCH₂CH₃ .619 Cl S OCH₂COOCH₂CH₃ .620 F S OCH₂COOCH₂CH₃ .621 F S OCH(CH₃)COOH .622 F S OCH(CH₃)COOCH₂CH₃ .623 F S OCH(CH₃)COOCH₂CCH .624 F S OCH₂C(O)NH₂ .625 F S OCH₂C(O)NH(CH₃) .626 F S OCH₂C(O)N(CH₂CH₃)₂ .627 F S OCH₂C(O)NH(CH₂CCH) .628 Cl S OCH₂C(O)N(CH₃)₂ .629 F S OCH₂C(O)N(CH₃)₂ .630 F S OCH₂C(O)N(CH₃)(CH₂(o-F—C₆H₄)) .631 Cl S OCH₂C(O)SCH₃ .632 F S OCH₂C(O)SCH₃ .633 F S OCH₂(O)SCH₂CH₃ .634 H S OCH₂C(O)SCH(CH₃)₂ .635 Cl S OCH₂C(O)SCH(CH₃)₂ .636 F S OCH₂C(O)SCH(CH₃)₂ .637 Cl S OCH₂C(O)SCH₂C₆H₅ .638 F S OCH(CH₃)C(O)SCH₂C₈H₅ .639 H S OCH₂CH₂OH .640 Cl S OCH₂CH₂OH .641 F S OCH₂CH₂OH .642 H S OCH₂CH(CH₃)OH .643 Cl S OCH₂CH(CH₃)OH .644 F S OCH₂CH(CH₃)OH .645 F S OCH₂CH₂Cl .646 F S OCH₂CF₃ .647 Cl S OCH₂CN .648 F S OCH₂CN .649 H S OCH₂CH₂CN .650 Cl S OCH₂CH₂CN .651 F S OCH₂CH₂CN .652 Cl S OCH₂CH₂CF₃ .653 F S OCH₂CH₂CF₃ .654 F S OCH₂CH(OH)(C₆H₅)

Table 38:

A preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₃₈.

Table 39:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₃₉.

Table 40:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₀.

Table 41:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₁.

Table 42

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₂.

Table 43:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₃.

Table 44:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₄.

Table 45:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B. thus disclosing 264 specific compounds of formula I₄₅.

Table 46:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₆.

Table 47:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₇.

Table 48:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₈.

Table 49:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₄₉.

Table 50:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₀.

Table 51:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₁.

Table 52:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₂.

Table 53:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₃.

Table 54:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₄.

Table 55:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₅.

Table 56:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table e, thus disclosing 264 specific compounds of formula I₅₆.

Table 57:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₇.

Table 58:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₈.

Table 59:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₅₉.

Table 60:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₀.

Table 61:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₈₁.

Table 62:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₂.

Table 63:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₃.

Table 64:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₄.

Table 65:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₅.

Table 66:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₆.

Table 67:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₇.

Table 68

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₈.

Table 69:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₆₉.

Table 70:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₇₀.

Table 71:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₇₁.

Table 72:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B. thus disclosing 264 specific compounds of formula I₇₂.

Table 73:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₇₃.

Table 74:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₇₄.

Table 75:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₇₅.

Table 76:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₇₆.

Table 77:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₇₇.

Table 78:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 254 specific compounds of formula I₇₈.

Table 79:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B. thus disclosing 264 specific compounds of formula I₇₉.

Table 80:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₈₀.

Table 81:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₈₁.

Table 82:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₈₂.

Table 83:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B. thus disclosing 264 specific compounds of formula I₈₃.

Table 84:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B. thus disclosing 264 specific compounds of formula I₈₄.

Table 85:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₈₅.

Table 86:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₈₆.

Table 87:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B. thus disclosing 264 specific compounds of formula I₈₇.

Table 88:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₃₂ are given in Table B, thus disclosing 264 specific compounds of formula I₈₈.

TABLE B Compd. No. R₁₁ R₁₂ R₃₂ or R₃₄ .001 H Cl H .002 Cl Cl H .003 F Cl H .004 H Br H .005 Cl Br H .006 F Br H .007 Cl CF₃ H .008 F CF₃ H .009 F CH₃ H .010 F OCF₃ H .011 H Cl CH₃ .012 Cl Cl CH₃ .013 F Cl CH₃ .014 H Br CH₃ .015 Cl Br CH₃ .016 F Br CH₃ .017 Cl CF₃ CH₃ .018 F CF₃ CH₃ .019 F CH₃ CH₃ .020 F OCF₃ CH₃ .021 H Cl CH₂CHCH₂ .022 Cl Cl CH₂CHCH₂ .023 F Cl CH₂CHCH₂ .024 H Br CH₂CHCH₂ .025 Cl Br CH₂CHCH₂ .026 F Br CH₂CHCH₂ .027 Cl CF₃ CH₂CHCH₂ .028 F CF₃ CH₂CHCH₂ .029 F CH₃ CH₂CHCH₂ .030 F OCF₃ CH₂CHCH₂ .031 H Cl CH₂CH(CH₃)₂ .032 Cl Cl CH₂CH(CH₃)₂ .033 F Cl CH₂CH(CH₃)₂ .034 H Br CH₂CH(CH₃)₂ .035 Cl Br CH₂CH(CH₃)₂ .036 F Br CH₂CH(CH₃)₂ .037 Cl CF₃ CH₂CH(CH₃)₂ .038 F CF₃ CH₂CH(CH₃)₂ .039 F CH₃ CH₂CH(CH₃)₂ .040 F OCF₃ CH₂CH(CH₃)₂ .041 H Cl CH₂CCH .042 Cl Cl CH₂CCH .043 F Cl CH₂CCH .044 H Br CH₂CCH .045 Cl Br CH₂CCH .046 F Br CH₂CCH .047 Cl CF₃ CH₂CCH .048 F CF₃ CH₂CCH .049 F CH₃ CH₂CCH .050 F OCF₃ CH₂CCH .051 H Cl CF₃ .052 Cl Cl CF₃ .053 F Cl CF₃ .054 H Br CF₃ .055 Cl Br CF₃ .056 F Br CF₃ .057 Cl CF₃ CF₃ .058 F CF₃ CF₃ .059 F CH₃ CF₃ .060 F OCF₃ CF₃ .061 H Cl CH₂Cl .062 Cl Cl CH₂Cl .063 F Cl CH₂Cl 064 H Br CH₂Cl .065 Cl Br CH₂Cl .066 F Br CH₂Cl .067 Cl CF₃ CH₂Cl .068 F CF₃ CH₂Cl .069 F CH₃ CH₂Cl .070 F OCF₃ CH₂Cl .071 H Cl CH₂CN .072 Cl Cl CH₂CN .073 F Cl CH₂CN .074 H Br CH₂CN .075 Cl Br CH₂CN .076 F Br CH₂CN .077 Cl CF₃ CH₂CN .078 F CF₃ CH₂CN .079 F CH₃ CH₂CN .080 F OCF₃ CH₂CN .081 H Cl CH₂OH .082 Cl Cl CH₂OH .083 F Cl CH₂OH .084 H Br CH₂OH .085 Cl Br CH₂OH .086 F Br CH₂OH .087 Cl CF₃ CH₂OH .088 F CF₃ CH₂OH .089 F CH₃ CH₂OH .090 F OCF₃ CH₂OH .091 H Cl CH₂OC(O)CH₃ .092 Cl Cl CH₂OC(O)CH₃ .093 F Cl CH₂OC(O)CH₃ .094 H Br CH₂OC(O)CH₃ .095 Cl Br CH₂OC(O)CH₃ .096 F Br CH₂OC(O)CH₃ .097 Cl CF₃ CH₂OC(O)CH₃ .098 F CF₃ CH₂OC(O)CH₃ .099 F CH₃ CH₂OC(O)CH₃ .100 F OCF₃ CH₂OC(O)CH₃ .101 H Cl CH₂OCH₂CHCH₂ .102 Cl Cl CH₂OCH₂CHCH₂ .103 F Cl CH₂OCH₂CHCH₂ .104 H Br CH₂OCH₂CHCH₂ .105 Cl Br CH₂OCH₂CHCH₂ .106 F Br CH₂OCH₂CHCH₂ .107 Cl CF₃ CH₂OCH₂CHCH₂ .108 F CF₃ CH₂OCH₂CHCH₂ .109 F CH₃ CH₂OCH₂CHCH₂ .110 F OCF₃ CH₂OCH₂CHCH₂ .111 H Cl COOH .112 Cl Cl COOH .113 F Cl COOH .114 H Br COOH .115 Cl Br COOH .116 F Br COOH .117 Cl CF₃ COOH .118 F CF₃ COOH .119 F CH₃ COOH .120 F OCF₃ COOH .121 H Cl COOCH₃ .122 Cl Cl COOCH₃ .123 F Cl COOCH₃ .124 H Br COOCH₃ .125 Cl Br COOCH₃ .126 F Br COOCH₃ .127 Cl CF₃ COOCH₃ .128 F CF₃ COOCH₃ .129 F CH₃ COOCH₃ .130 F OCF₃ COOCH₃ .131 H Cl COOCH₂CH₃ .132 Cl Cl COOCH₂CH₃ .133 F Cl COOCH₂CH₃ .134 H Br COOCH₂CH₃ .135 Cl Br COOCH₂CH₃ .136 F Br COOCH₂CH₃ .137 Cl CF₃ COOCH₂CH₃ .138 F CF₃ COOCH₂CH₃ .139 F CH₃ COOCH₂CH₃ .140 F OCF₃ COOCH₂CH₃ .141 Cl Cl COOCH(CH₃)₂ .142 F Cl COOCH(CH₃)₂ .143 H Br COOCH(CH₃)₂ .144 Cl Br COOCH(CH₃)₂ .145 F Br COOCH(CH₃)₂ .146 Cl CF₃ COOCH(CH₃)₂ .147 F CF₃ COOCH(CH₃)₂ .148 F CH₃ COOCH(CH₃)₂ .149 F OCF₃ COOCH(CH₃)₂ .150 F Cl COOCH₂CHCH₂ .151 F Cl COOCH₂CCH .152 F Cl COOCH₂(o-F-C₆H₅) .153 H Cl COOCH₂C₆H₅ .154 Cl Cl COOCH₂C₆H₅ .155 F Cl COOCH₂C₆H₅ .156 H Br COOCH₂C₆H₅ .157 Cl Br COOCH₂C₆H₅ .158 F Br COOCH₂C₆H₅ .159 Cl CF₃ COOCH₂C₆H₅ .160 F CF₃ COOCH₂C₆H₅ .161 F CH₃ COOCH₂C₆H₅ .162 F OCF₃ COOCH₂C₆H₅ .163 F Cl COOCH₂CH₂Cl .164 H Cl COSCH(CH₃)₂ .165 Cl Cl COSCH(CH₃)₂ .166 F Cl COSCH(CH₃)₂ .167 H Br COSCH(CH₃)₂ .168 Cl Br COSCH(CH₃)₂ .169 F Br COSCH(CH₃)₂ .170 Cl CF₃ COSCH(CH₃)₂ .171 F CF₃ COSCH(CH₃)₂ .172 F CH₃ COSCH(CH₃)₂ .173 F OCF₃ COSCH(CH₃)₂ 174 H Cl CONHCH₂CCH .175 Cl Cl CONHCH₂CCH .176 F Cl CONHCH₂CCH .177 H Br CONHCH₂CCH .178 Cl Br CONHCH₂CCH .179 F Br CONHCH₂CCH .180 Cl CF₃ CONHCH₂CCH .181 F CF₃ CONHCH₂CCH .182 F CH₃ CONHCH₂CCH .183 F OCF₃ CONHCH₂CCH .184 H Cl CON(CH₂CH₃)₂ .185 Cl Cl CON(CH₂CH₃)₂ .186 F Cl CON(CH₂CH₃)₂ .187 H Br CON(CH₂CH₃)₂ .188 Cl Br CON(CH₂CH₃)₂ .189 F Br CON(CH₂CH₃)₂ .190 Cl CF₃ CON(CH₂CH₃)₂ .191 F CF₃ CON(CH₂CH₃)₂ .192 F CH₃ CON(CH₂CH₃)₂ .193 F OCF₃ CON(CH₂CH₃)₂ .194 F Cl CON(CH₂CHCH₂)₂ .195 F Cl CON(CH₂CH₃)CH₂CHCH₂ .196 F Cl CONHCH₂CH(CH₃)₂ .197 F Cl CONH(SO₂CH₃) .198 H Cl CHO .199 Cl Cl CHO .200 F Cl CHO .201 H Br CHO .202 Cl Br CHO .203 F Br CHO .204 Cl CF₃ CHO .205 F CF₃ CHO .206 F CH₃ CHO .207 F OCF₃ CHO .208 H Cl CHNOH .209 Cl Cl CHNOH .210 F Cl CHNOH .211 H Br CHNOH .212 Cl Br CHNOH .213 F Br CHNOH .214 Cl CF₃ CHNOH .215 F CF₃ CHNOH .216 F CH₃ CHNOH .217 F OCF₃ CHNOH .218 H Cl CHNOCH₂CCH .219 Cl Cl CHNOCH₂CCH .220 F Cl CHNOCH₂CCH .221 H Br CHNCCH₂CCH .222 Cl Br CHNOCH₂CCH .223 F Br CHNOCH₂CCH .224 Cl CF₃ CHNOCH₂CCH .225 F CF₃ CHNOCH₂CCH .226 F CH₃ CHNOCH₂CCH .227 F OCF₃ CHNOCH₂CCH .228 F Cl CHNOCH₃ .229 F Cl CHNOCH₂CHCH₂ .230 H Cl CH₂COOH .231 Cl Cl CH₂COOH .232 F Cl CH₂COOH .233 H Br CH₂COOH .234 Cl Br CH₂COOH .235 F Br CH₂COOH .236 Cl CF₃ CH₂COOH .237 F CF₃ CH₂COOH .238 F CH₃ CH₂COOH .239 F OCF₃ CH₂COOH .240 F Cl CH₂COOCH₃ .241 F Cl CH₂COOCH(CH₃)₂ .242 F Cl CH₂COOCH₂CHCH₂ .243 H Cl CH₂CH₂COOH .244 Cl Cl CH₂CH₂COOH .245 F Cl CH₂CH₂COOH .246 H Br CH₂CH₂COOH .247 Cl Br CH₂CH₂COOH .248 F Br CH₂CH₂COOH .249 Cl CF₃ CH₂CH₂COOH .250 F CF₃ CH₂CH₂COOH .251 F CH₃ CH₂CH₂COOH .252 F OCF₃ CH₂CH₂COOH .253 F Cl CH₂CH₂COOCH₂CH₃ .254 F Cl CH₂CH₂COOCH(CH₃)₂ .255 F Cl CH₂CH₂COOCH₂CHCH₂ .256 F Cl CH₂CH₂COOCH₂C(CH₃)CH₂ .257 F Cl CH₂CH₂COOCH₂CCH .258 F Cl CH₂CH₂COOCH(CH₃)CCH .259 F Cl CH(OH)CH₃ .260 F Cl C(O)CH₃ .261 F Cl CN .262 Cl CF₃ CN .263 F Cl C(S)NH₂ .264 Cl CF₃ C(S)NH₂

Table 89:

A preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₈₉.

Table 90:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₀.

Table 91:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₁.

Table 92:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₂.

Table 93:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₃.

Table 94:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus do sing 627 specific compounds of formula I₉₄.

Table 95:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₅.

Table 96:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₆.

Table 97:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₇.

Table 98:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₈.

Table 99:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₉₉.

Table 100:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₀.

Table 101:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₂.

Table 102:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₂.

Table 103:

Another preferred group of compounds of formula I corresponds to the general formula

in which tire sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₃.

Table 104:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₄.

Table 105:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₅.

Table 106:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₆.

Table 107:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₇.

Table 108:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₈.

Table 109:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₀₉.

Table 110:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₀.

Table 111:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₁.

Table 112:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₂.

Table 113:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₃.

Table 114:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₄.

Table 115:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₅.

Table 116:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₆.

Table 117:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₇.

Table 118:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₈.

Table 119:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets cf correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₁₉.

Table 120:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₀.

Table 121:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₁.

Table 122:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₂.

Table 123:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₃.

Table 124:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₄.

Table 125:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₅.

Table 126:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₆.

Table 127:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₇.

Table 128:

Another preferred group of compounds of formula I corresponds to the genera; formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₈.

Table 129:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₂₉.

Table 130:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₀.

Table 131:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₁.

Table 132:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₂.

Table 133:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₃.

Table 134:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C. thus disclosing 627 specific compounds of formula I₁₃₄.

Table 135:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₅.

Table 136:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₆.

Table 137:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₇.

Table 138:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₈.

Table 139:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₃₉.

Table 140:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₄₀.

Table 141:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₄₁.

Table 142:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table C, thus disclosing 627 specific compounds of formula I₁₄₂.

TABLE C Compd. No. R₁₁ R₁₂ R₁₃ .001 H Cl CH₂CHCH₂ .002 Cl Cl CH₂CHCH₂ .003 F Cl CH₂CHCH₂ .004 H Br CH₂CHCH₂ .005 Cl Br CH₂CHCH₂ .006 F Br CH₂CHCH₂ .007 H I CH₂CHCH₂ .008 Cl I CH₂CHCH₂ .009 F I CH₂CHCH₂ .010 H CH₃ CH₂CHCH₂ .011 Cl CH₃ CH₂CHCH₂ .012 F CH₃ CH₂CHCH₂ .013 H OH CH₂CHCH₂ .014 Cl OH CH₂CHCH₂ .015 F OH CH₂CHCH₂ .016 H OCF₃ CH₂CHCH₂ .017 Cl OCF₃ CH₂CHCH₂ .018 F OCF₃ CH₂CHCH₂ .019 H CHO CH₂CHCH₂ .020 Cl CHO CH₂CHCH₂ .021 F CHO CH₂CHCH₂ .022 H CHF₂ CH₂CHCH₂ .023 Cl CHF₂ CH₂CHCH₂ .024 F CHF₂ CH₂CHCH₂ .025 H COOH CH₂CHCH₂ .026 Cl COOH CH₂CHCH₂ .027 F COOH CH₂CHCH₂ .028 H COOCH₂CH₃ CH₂CHCH₂ .029 Cl COOCH₂CH₃ CH₂CHCH₂ .030 F COOCH₂CH₃ CH₂CHCH₂ .031 H CN CH₂CHCH₂ .032 Cl CN CH₂CHCH₂ .033 F CN CH₂CHCH₂ .034 H Cl CH₂C₆H₅ .035 Cl Cl CH₂C₆H₅ .036 F Cl CH₂C₆H₅ .037 H Br CH₂C₆H₅ .038 Cl Br CH₂C₆H₅ .039 F Br CH₂C₆H₅ .040 H I CH₂C₆H₅ .041 Cl I CH₂C₆H₅ .042 F I CH₂C₆H₅ .043 H CH₃ CH₂C₆H₅ .044 Cl CH₃ CH₂C₆H₅ .045 F CH₃ CH₂C₆H₅ .046 H OH CH₂C₆H₅ .047 Cl OH CH₂C₆H₅ .048 F OH CH₂C₆H₅ .049 H OCF₃ CH₂C₆H₅ .050 Cl OCF₃ CH₂C₆H₅ .051 F OCF₃ CH₂C₆H₅ .052 H CHO CH₂C₆H₅ .053 Cl CHO CH₂C₆H₅ .054 F CHO CH₂C₆H₅ .055 H CHF₂ CH₂C₆H₅ .056 Cl CHF₂ CH₂C₆H₅ .057 F CHF₂ CH₂C₆H₅ .058 H COOH CH₂C₆H₅ .059 Cl COOH CH₂C₆H₅ .060 F COOH CH₂C₆H₅ .061 H COOCH₂CH₃ CH₂C₆H₅ .062 Cl COOCH₂CH₃ CH₂C₆H₅ .063 F COOCH₂CH₃ CH₂C₆H₅ .064 H CN CH₂C₆H₅ .065 Cl CN CH₂C₆H₅ .066 F CN CH₂C₆H₅ .067 H Cl CH₂CCH .068 Cl Cl CH₂CCH .069 F Cl CH₂CCH .070 H Br CH₂CCH .071 Cl Br CH₂CCH .072 F Br CH₂CCH .073 H I CH₂CCH .074 Cl I CH₂CCH .075 F I CH₂CCH .076 H CH₃ CH₂CCH .077 Cl CH₃ CH₂CCH .078 F CH₃ CH₂CCH .079 H OH CH₂CCH .080 Cl OH CH₂CCH .081 F OH CH₂CCH .082 H OCF₃ CH₂CCH .083 Cl OCF₃ CH₂CCH .084 F OCF₃ CH₂CCH .085 H CHO CH₂CCH .086 Cl CHO CH₂CCH .087 F CHO CH₂CCH .088 H CHF₂ CH₂CCH .089 Cl CHF₂ CH₂CCH .090 F CHF₂ CH₂CCH .091 H COOH CH₂CCH .092 Cl COOH CH₂CCH .093 F COOH CH₂CCH .094 H COOCH₂CH₃ CH₂CCH .095 Cl COOCH₂CH₃ CH₂CCH .096 F COOCH₂CH₃ CH₂CCH .097 H CN CH₂CCH .098 Cl CN CH₂CCH .099 F CN CH₂CCH .100 H Cl CH₂COOH .101 Cl Cl CH₂COOH .102 F Cl CH₂COOH .103 H Br CH₂COOH .104 Cl Br CH₂COOH .105 F Br CH₂COOH .106 H I CH₂COOH .107 Cl 1 CH₂COOH .108 F I CH₂COOH .109 H CH₃ CH₂COOH .110 Cl CH₃ CH₂COOH .111 F CH₃ CH₂COOH .112 H OH CH₂COOH .113 Cl OH CH₂COOH .114 F OH CH₂COOH .115 H OCF₃ CH₂COOH .116 Cl OCF₃ CH₂COOH .117 F OCF₃ CH₂COOH .118 H CHO CH₂COOH .119 Cl CHO CH₂COOH .120 F CHO CH₂COOH .121 H CHF₂ CH₂COOH .122 Cl CHF₂ CH₂COOH .123 F CHF₂ CH₂COOH .124 H COOH CH₂COOH .125 Cl COOH CH₂COOH .126 F COOH CH₂COOH .127 H COOCH₂CH₃ CH₂COOH .128 Cl COOCH₂CH₃ CH₂COOH .129 F COOCH₂CH₃ CH₂COOH .130 H CN CH₂COOH .131 Cl CN CH₂COOH .132 F CN CH₂COOH .133 H Cl CH₂COOCH₃ .134 Cl Cl CH₂COOCH₃ .135 F Cl CH₂COOCH₃ .136 H Br CH₂COOCH₃ .137 Cl Br CH₂COOCH₃ .138 F Br CH₂COOCH₃ .139 H I CH₂COOCH₃ .140 Cl I CH₂COOCH₃ .141 F I CH₂COOCH₃ .142 H CH₃ CH₂COOCH₃ .143 Cl CH₃ CH₂COOCH₃ .144 F CH₃ CH₂COOCH₃ .145 H OH CH₂COOCH₃ .146 Cl OH CH₂COOCH₃ .147 F OH CH₂COOCH₃ .148 H OCF₃ CH₂COOCH₃ .149 Cl OCF₃ CH₂COOCH₃ .150 F OCF₃ CH₂COOCH₃ .151 H CHO CH₂COOCH₃ .152 Cl CHO CH₂COOCH₃ .153 F CHO CH₂COOCH₃ .154 H CHF₂ CH₂COOCH₃ .155 Cl CHF₂ CH₂COOCH₃ .156 F CHF₂ CH₂COOCH₃ .157 H COOH CH₂COOCH₃ .158 Cl COOH CH₂COOCH₃ .159 F COOH CH₂COOCH₃ .160 H COOCH₂CH₃ CH₂COOCH₃ .161 Cl COOCH₂CH₃ CH₂COOCH₃ .162 F COOCH₂CH₃ CH₂COOCH₃ .163 H CN CH₂COOCH₃ .164 Cl CN CH₂COOCH₃ .165 F CN CH₂COOCH₃ .166 H Cl OH .167 Cl Cl OH .168 F Cl OH .169 H Br OH .170 Cl Br OH .171 F Br OH .172 H I OH .173 Cl I OH .174 F I OH .175 H CH₃ OH .176 Cl CH₃ OH .177 F CH₃ OH .178 H OH OH .179 Cl OH OH .180 F OH OH .181 H OCF₃ OH .182 Cl OCF₃ OH .183 F OCF₃ OH .184 H CHO OH .185 Cl CHO OH .186 F CHO OH .187 H CHF₂ OH .188 Cl CHF₂ OH .189 F CHF₂ OH .190 H COOH OH .191 Cl COOH OH .192 F COOH OH .193 H COOCH₂CH₃ OH .194 Cl COOCH₂CH₃ OH .195 F COCCH₂CH₃ OH .196 H CN OH .197 Cl CN OH .198 F CN OH .199 H Cl OCH₂CHCH₂ .200 Cl Cl OCH₂CHCH₂ .201 F Cl OCH₂CHCH₂ .202 H Br OCH₂CHCH₂ .203 Cl Br OCH₂CHCH₂ .204 F Br OCH₂CHCH₂ .205 H I OCH₂CHCH₂ .206 Cl I OCH₂CHCH₂ .207 F I OCH₂CHCH₂ .208 H CH₃ OCH₂CHCH₂ .209 Cl CH₃ OCH₂CHCH₂ .210 F CH₃ OCH₂CHCH₂ .211 H OH OCH₂CHCH₂ .212 Cl OH OCH₂CHCH₂ .213 F OH OCH₂CHCH₂ .214 H OCF₃ OCH₂CHCH₂ .215 Cl OCF₃ OCH₂CHCH₂ .216 F OCF₃ OCH₂CHCH₂ .217 H CHO OCH₂CHCH₂ .218 Cl CHO OCH₂CHCH₂ .219 F CHO OCH₂CHCH₂ .220 H CHF₂ OCH₂CHCH₂ .221 Cl CHF₂ OCH₂CHCH₂ .222 F CHF₂ OCH₂CHCH₂ .223 H COOH OCH₂CHCH₂ .224 Cl COOH OCH₂CHCH₂ .225 F COOH OCH₂CHCH₂ .226 H COOCH₂CH₃ OCH₂CHCH₂ .227 Cl COOCH₂CH₃ OCH₂CHCH₂ .228 F COOCH₂CH₃ OCH₂CHCH₂ .229 H CN OCH₂CHCH₂ .230 Cl CN OCH₂CHCH₂ .231 F CN OCH₂CHCH₂ .232 H Cl OCH₂C₆H₅ .233 Cl Cl OCH₂C₆H₅ .234 F Cl OCH₂C₆H₅ .235 H Br OCH₂C₆H₅ .236 Cl Br OCH₂C₆H₅ .237 F Br OCH₂C₆H₅ .238 H I OCH₂C₆H₅ .239 Cl I OCH₂C₆H₅ .240 F I OCH₂C₆H₅ .241 H CH₃ OCH₂C₆H₅ .242 Cl CH₃ OCH₂C₆H₅ .243 F CH₃ OCH₂C₆H₅ .244 H OH OCH₂C₆H₅ .245 Cl OH OCH₂C₆H₅ .246 F OH OCH₂C₆H₅ .247 H OCF₃ OCH₂C₆H₅ .248 Cl OCF₃ OCH₂C₆H₅ .249 F OCF₃ OCH₂C₆H₅ .250 H CHO OCH₂C₆H₅ .251 Cl CHO OCH₂C₆H₅ .252 F CHO OCH₂C₆H₅ .253 H CHF₂ OCH₂C₆H₅ .254 Cl CHF₂ OCH₂C₆H₅ .255 F CHF₂ OCH₂C₆H₅ .256 H COOH OCH₂C₆H₅ .257 Cl COOH OCH₂C₆H₅ .258 F COOH OCH₂C₆H₅ .259 H COOCH₂CH₃ OCH₂C₆H₅ .260 Cl COOCH₂CH₃ OCH₂C₆H₅ .261 F COOCH₂CH₃ OCH₂C₆H₅ .262 H CN OCH₂C₆H₅ .263 Cl CN OCH₂C₆H₅ .264 F CN OCH₂C₆H₅ .265 H Cl OCH₂COOH .266 Cl Cl OCH₂COOH .267 F Cl OCH₂COOH .268 H Br OCH₂COOH .269 Cl Br OCH₂COOH .270 F Br OCH₂COOH .271 H I OCH₂COOH .272 Cl I OCH₂COOH .273 F I OCH₂COOH .274 H CH₃ OCH₂COOH .275 Cl CH₃ OCH₂COOH .276 F CH₃ OCH₂COOH .277 H OH OCH₂COOH .278 Cl OH OCH₂COOH .279 F OH OCH₂COOH .280 H OCF₃ OCH₂COOH .281 Cl OCF₃ OCH₂COOH .282 F OCF₃ OCH₂COOH .283 H CHO OCH₂COOH .284 Cl CHO OCH₂COOH .285 F CHO OCH₂COOH .286 H CHF₂ OCH₂COOH .287 Cl CHF₂ OCH₂COOH .288 F CHF₂ OCH₂COOH .289 H COOH OCH₂COOH .290 Cl COOH OCH₂COOH .291 F COOH OCH₂COOH .292 H COOCH₂CH₃ OCH₂COOH .293 Cl COOCH₂CH₃ OCH₂COOH .294 F COOCH₂CH₃ OCH₂COOH .295 H CN OCH₂COOH .296 Cl CN OCH₂COOH .297 F CN OCH₂COOH .298 H Cl OCH₂COOCH₃ .299 Cl Cl OCH₂COOCH₃ .300 F Cl OCH₂COOCH₃ .301 H Br OCH₂COOCH₃ .302 Cl Br OCH₂COOCH₃ .303 F Br OCH₂COQCH₃ .304 H I OCH₂COOCH₃ .305 Cl I OCH₂COOCH₃ .306 F I OCH₂COOCH₃ .307 H CH₃ OCH₂COOCH₃ .308 Cl CH₃ OCH₂COOCH₃ .309 F CH₃ OCH₂COOCH₃ .310 H OH OCH₂COOCH₃ .311 Cl OH OCH₂COOCH₃ .312 F OH OCH₂COOCH₃ .313 H OCF₃ OCH₂COOCH₃ .314 Cl OCF₃ OCH₂COOCH₃ .315 F OCF₃ OCH₂COOCH₃ .316 H CHO OCH₂COOCH₃ .317 Cl CHO OCH₂COOCH₃ .318 F CHO OCH₂COOCH₃ .319 H CHF₂ OCH₂COOCH₃ .320 Cl CHF₂ OCH₂COOOH₃ .321 F CHF₂ OCH₂COOCH₃ .322 H COOH OCH₂COOCH₃ .323 Cl COOH OCH₂COOCH₃ .324 F COOH OCH₂COOCH₃ .325 H COOCH₂CH₃ OCH₂COOCH₃ .326 Cl COOCH₂CH₃ OCH₂COOCH₃ .327 F COOCH₂CH₃ OCH₂COOCH₃ .328 H CN OCH₂COOCH₃ .329 Cl CN OCH₂COOCH₃ .330 F CN QCH₂COOCH₃ .331 H Cl CH₂CHO .332 Cl Cl CH₂CHO .333 F Cl CH₂CHO .334 H Br CH₂CHO .335 Cl Br CH₂CHO .336 F Br CH₂CHO .337 H I CH₂CHO .338 Cl I CH₂CHO .339 F I CH₂CHO .340 H CH₃ CH₂CHO .341 Cl CH₃ CH₂CHO .342 F CH₃ CH₂CHO .343 H OH CH₂CHO .344 Cl OH CH₂CHO .345 F OH CH₂CHO .346 H OCF₃ CH₂CHO .347 Cl OCF₃ CH₂CHO .348 F OCF₃ CH₂CHO .349 H CHO CH₂CHO .350 Cl CHO CH₂CHO .351 F CHO CH₂CHO .352 H CHF₂ CH₂CHO .353 Cl CHF₂ CH₂CHO .354 F CHF₂ CH₂CHO .355 H COOH CH₂CHO .356 Cl COOH CH₂CHO .357 F COOH CH₂CHO .358 H COOCH₂CH₃ CH₂CHO .359 Cl COOCH₂CH₃ CH₂CHO .360 F COOCH₂CH₃ CH₂CHO .361 H CN CH₂CHO .362 Cl CN CH₂CHO .363 F CN CH₂CHO .364 H Cl OCH₂CHO .365 Cl Cl OCH₂CHO .366 F Cl OCH₂CHO .367 H Br OCH₂CHO .368 Cl Br OCH₂CHO .369 F Br OCH₂CHO .370 H I OCH₂CHO .371 Cl I OCH₂CHO .372 F I OCH₂CHO .373 H CH₃ OCH₂CHO .374 Cl CH₃ OCH₂CHO .375 F CH₃ OCH₂CHO .376 H OH OCH₂CHO .377 Cl OH OCH₂CHO .378 F OH OCH₂CHO .379 H OCF₃ OCH₂CHO .380 Cl OCF₃ OCH₂CHO .381 F OCF₃ OCH₂CHO .382 H CHO OCH₂CHO .383 Cl CHO OCH₂CHO .384 F CHO OCH₂CHO .385 H CHF₂ OCH₂CHO .386 Cl CHF₂ OCH₂CHO .387 F CHF₂ OCH₂CHO .388 H COOH OCH₂CHO .389 Cl COOH OCH₂CHO .390 F COOH OCH₂CHO .391 H COOCH₂CH₃ OCH₂CHO .392 Cl COOCH₂CH₃ OCH₂CHO .393 F COOCH₂CH₃ OCH₂CHO .394 H CN OCH₂CHO .395 Cl CN OCH₂CHO .396 F CN OCH₂CHO .397 H Cl OCH₃ .398 Cl Cl OCH₃ .399 F Cl OCH₃ .400 H Br OCH₃ .401 Cl Br OCH₃ .402 F Br OCH₃ .403 H I OCH₃ .404 Cl I OCH₃ .405 F I OCH₃ .406 H CH₃ OCH₃ .407 Cl CH₃ OCH₃ .408 F CH₃ OCH₃ .409 H OH OCH₃ .410 Cl OH OCH₃ .411 F OH OCH₃ .412 H OCF₃ OCH₃ .413 Cl OCF₃ OCH₃ .414 F OCF₃ OCH₃ .415 H CHO OCH₃ .416 Cl CHO OCH₃ .417 F CHO OCH₃ .418 H CHF₂ OCH₃ .419 Cl CHF₂ OCH₃ .420 F CHF₂ OCH₃ .421 H COOH OCH₃ .422 Cl COOH OCH₃ .423 F COOH OCH₃ .424 H COOCH₂CH₃ OCH₃ .425 Cl COOCH₂CH₃ OCH₃ .426 F COOCH₂CH₃ OCH₃ .427 H CN OCH₃ .428 Cl CN OCH₃ .429 F CN OCH₃ .430 H Cl CH₂OCH₃ .431 Cl Cl CH₂OCH₃ .432 F Cl CH₂OCH₃ .433 H Br CH₂OCH₃ .434 Cl Br CH₂OCH₃ .435 F Br CH₂OCH₃ .436 H I CH₂OCH₃ .437 Cl I CH₂OCH₃ .438 F I CH₂OCH₃ .439 H CH₃ CH₂OCH₃ .440 Cl CH₃ CH₂OCH₃ .441 F CH₃ CH₂OCH₃ .442 H OH CH₂OCH₃ .443 Cl OH CH₂OCH₃ .444 F OH CH₂OCH₃ .445 H OCF₃ CH₂OCH₃ .446 Cl OCF₃ CH₂OCH₃ .447 F OCF₃ CH₂OCH₃ .448 H CHO CH₂OCH₃ .449 Cl CHO CH₂OCH₃ .450 F CHO CH₂OCH₃ .451 H CHF₂ CH₂OCH₃ .452 Cl CHF₂ CH₂OCH₃ .453 F CHF₂ CH₂OCH₃ .454 H COOH CH₂OCH₃ .455 Cl COOH CH₂OCH₃ .456 F COOH CH₂OCH₃ .457 H COOCH₂CH₃ CH₂OCH₃ .458 Cl COOCH₂CH₃ CH₂OCH₃ .459 F COOCH₂CH₃ CH₂OCH₃ .460 H CN CH₂OCH₃ .461 Cl CN CH₂OCH₃ .462 F CN CH₂OCH₃ .463 H Cl CH₂SCH₃ .464 Cl Cl CH₂SCH₃ .465 F Cl CH₂SCH₃ .466 H Br CH₂SCH₃ .467 Cl Br CH₂SCH₃ .468 F Br CH₂SCH₃ .469 H I CH₂SCH₃ .470 Cl I CH₂SCH₃ .471 F I CH₂SCH₃ .472 H CH₃ CH₂SCH₃ .473 Cl CH₃ CH₂SCH₃ .474 F CH₃ CH₂SCH₃ .475 H OH CH₂SCH₃ .476 Cl OH CH₂SCH₃ .477 F OH CH₂SCH₃ .478 H OCF₃ CH₂SCH₃ .479 Cl OCF₃ CH₂SCH₃ .480 F OCF₃ CH₂SCH₃ .481 H CHO CH₂SCH₃ .482 Cl CHO CH₂SCH₃ .483 F CHO CH₂SCH₃ .484 H CHF₂ CH₂SCH₃ .485 Cl CHF₂ CH₂SCH₃ .486 F CHF₂ CH₂SCH₃ .487 H COOH CH₂SCH₃ .488 Cl COOH CH₂SCH₃ .489 F COOH CH₂SCH₃ .490 H COOCH₂CH₃ CH₂SCH₃ .491 Cl COOCH₂CH₃ CH₂SCH₃ .492 F COOCH₂CH₃ CH₂SCH₃ .493 H CN CH₂SCH₃ .494 Cl CN CH₂SCH₃ .495 F CN CH₂SCH₃ .496 H Cl OCH₂OCH₃ .497 Cl Cl OCH₂OCH₃ .498 F Cl OCH₂OCH₃ .499 H Br OCH₂OCH₃ .500 Cl Br OCH₂OCH₃ .501 F Br OCH₂OCH₃ .502 H I OCH₂OCH₃ .503 Cl I OCH₂OCH₃ .504 F I OCH₂OCH₃ .505 H CH₃ OCH₂OCH₃ .506 Cl CH₃ OCH₂OCH₃ .507 F CH₃ OCH₂OCH₃ .508 H OH OCH₂OCH₃ .509 Cl OH OCH₂OCH₃ .510 F OH OCH₂OCH₃ .511 H OCF₃ OCH₂OCH₃ .512 Cl OCF₃ OCH₂OCH₃ .513 F OCF₃ OCH₂OCH₃ .514 H CHO OCH₂OCH₃ .515 Cl CHO OCH₂OCH₃ .516 F CHO OCH₂OCH₃ .517 H CHF₂ OCH₂OCH₃ .518 Cl CHF₂ OCH₂OCH₃ .519 F CHF₂ OCH₂OCH₃ .520 H COOH OCH₂OCH₃ .521 Cl COOH OCH₂OCH₃ .522 F COOH OCH₂OCH₃ .523 H COOCH₂CH₃ OCH₂OCH₃ .524 Cl COOCH₂CH₃ OCH₂OCH₃ .525 F COOCH₂CH₃ OCH₂OCH₃ .526 H CN OCH₂OCH₃ .527 Cl CN OCH₂OCH₃ .528 F CN OCH₂OCH₃ .529 H Cl OCH₂SCH₃ .530 Cl Cl OCH₂SCH₃ .531 F Cl OCH₂SCH₃ .532 H Br OCH₂SCH₃ .533 Cl Br OCH₂SCH₃ .534 F Br OCH₂SCH₃ .535 H I OCH₂SCH₃ .536 Cl I OCH₂SCH₃ .537 F I OCH₂SCH₃ .538 H CH₃ OCH₂SCH₃ .539 Cl CH₃ OCH₂SCH₃ .540 F CH₃ OCH₂SCH₃ .541 H OH OCH₂SCH₃ .542 Cl OH OCH₂SCH₃ .543 F OH OCH₂SCH₃ .544 H OCF₃ OCH₂SCH₃ .545 Cl OCF₃ OCH₂SCH₃ .546 F OCF₃ OCH₂SCH₃ .547 H CHO OCH₂SCH₃ .548 Cl CHO OCH₂SCH₃ .549 F CHO OCH₂SCH₃ .550 H CHF₂ OCH₂SCH₃ .551 Cl CHF₂ OCH₂SCH₃ .552 F CHF₂ OCH₂SCH₃ .553 H COOH OCH₂SCH₃ .554 Cl COOH OCH₂SCH₃ .555 F COOH OCH₂SCH₃ .556 H COOCH₂CH₃ OCH₂SCH₃ .557 Cl COOCH₂CH₃ OCH₂SCH₃ .558 F COOCH₂CH₃ OCH₂SCH₃ .559 H CN OCH₂SCH₃ .560 Cl CN OCH₂SCH₃ .561 F CN OCH₂SCH₃ .562 H Cl OCH₂CH₂CN .563 Cl Cl OCH₂CH₂CN .564 F Cl OCH₂CH₂CN .565 H Br OCH₂CH₂CN .566 Cl Br OCH₂CH₂CN .567 F Br OCH₂CH₂CN .568 H I OCH₂CH₂CN .569 Cl I OCH₂CH₂CN .570 F I OCH₂CH₂CN .571 H CH₃ OCH₂CH₂CN .572 Cl CH₃ OCH₂CH₂CN .573 F CH₃ OCH₂CH₂CN .574 H OH OCH₂CH₂CN .575 Cl OH OCH₂CH₂CN .576 F OH OCH₂CH₂CN .577 H OCF₃ OCH₂CH₂CN .578 Cl OCF₃ OCH₂CH₂CN .579 F OCF₃ OCH₂CH₂CN .580 H CHO OCH₂CH₂CN .581 Cl CHO OCH₂CH₂CN .582 F CHO OCH₂CH₂CN .583 H CHF₂ OCH₂CH₂CN .584 Cl CHF₂ OCH₂CH₂CN .585 F CHF₂ OCH₂CH₂CN .586 H COOH OCH₂CH₂CN .587 Cl COOH OCH₂CH₂CN .588 F COOH OCH₂CH₂CN .589 H COOCH₂CH₃ OCH₂CH₂CN .590 Cl COOCH₂CH₃ OCH₂CH₂CN .591 F COOCH₂CH₃ OCH₂CH₂CN .592 H CN OCH₂CH₂CN .593 Cl CN OCH₂CH₂CN .594 F CN OCH₂CH₂CN .595 H Cl CH₂CH₂CN .596 Cl Cl CH₂CH₂CN .597 F Cl CH₂CH₂CN .598 H Br CH₂CH₂CN .599 Cl Br CH₂CH₂CN .600 F Br CH₂CH₂CN .601 H I CH₂CH₂CN .602 Cl I CH₂CH₂CN .603 F I CH₂CH₂CN .604 H CH₃ CH₂CH₂CN .605 Cl CH₃ CH₂CH₂CN .606 F CH₃ CH₂CH₂CN .607 H OH CH₂CH₂CN .608 Cl OH CH₂CH₂CN .609 F OH CH₂CH₂CN .610 H OCF₃ CH₂CH₂CN .611 Cl OCF₃ CH₂CH₂CN .612 F OCF₃ CH₂CH₂CN .613 H CHO CH₂CH₂CN .614 Cl CHO CH₂CH₂CN .615 F CHO CH₂CH₂CN .616 H CHF₂ CH₂CH₂CN .617 Cl CHF₂ CH₂CH₂CN .618 F CHF₂ CH₂CH₂CN .619 H COOH CH₂CH₂CN .620 Cl COOH CH₂CH₂CN .621 F COOH CH₂CH₂CN .622 H COOCH₂CH₃ CH₂CH₂CN .623 Cl COOCH₂CH₃ CH₂CH₂CN .624 F COOCH₂CH₃ CH₂CH₂CN .625 H CN CH₂CH₂CN .626 Cl CN CH₂CH₂CN .627 F CN CH₂CH₂CN

Table 143:

A preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₄₃.

Table 144:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₄₄.

Table 145:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₄₅.

Table 146:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₄₆.

Table 147:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₄₇.

Table 148:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₄₈.

Table 149:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₄₉.

Table 150:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₅₀.

Table 151:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₁₅.

Table 152:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₅₂.

Table 153:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₅₃.

Table 154:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₅₄.

Table 155:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₅₅.

Table 156:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₅₆.

Table 157:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 327 specific compounds of formula I₁₁₇.

Table 158:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₅₈.

Table 159:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₅₉.

Table 160:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₀.

Table 161:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₁.

Table 162:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₂.

Table 163:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₃.

Table 164:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₄.

Table 165:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₅.

Table 166:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₆.

Table 167:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₇.

Table 168:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₈.

Table 169:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₆₉.

Table 170:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₀.

Table 171:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₁.

Table 172:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₂.

Table 173:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₃.

Table 174:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₄.

Table 175:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₅.

Table 176:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₆.

Table 177:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₇.

Table 178:

Another preferred group of compounds of formula I corresponds to the general formula

in which the rets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₈.

Table 179:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₇₉.

Table 180:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₀.

Table 181:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ ate given in Table D, thus disclosing 627 specific compounds of formula I₁₈₁.

Table 182:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₂.

Table 183:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₃.

Table 184:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₄.

Table 185:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₅.

Table 186:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₆.

Table 187:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₇.

Table 188:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₈.

Table 189:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₈₉.

Table 190:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₉₀.

Table 191:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₉₁.

Table 192:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₉₂.

Table 193:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₉₃.

Table 194:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₉₄.

Table 195:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₉₅.

Table 196:

Another preferred group of compounds of formula I corresponds to the general formula

in which the sets of correlated substituents R₁₁, R₁₂ and R₁₃ are given in Table D, thus disclosing 627 specific compounds of formula I₁₉₆.

TABLE D Compd. No. R₁₁ H₁₂ R₁₃ .001 H Cl CH₂CHCH₂ .002 Cl Cl CH₂CHCH₂ .003 F Cl CH₂CHCH₂ .004 H Br CH₂CHCH₂ .005 Cl Br CH₂CHCH₂ .006 F Br CH₂CHCH₂ .007 H I CH₂CHCH₂ .008 Cl I CH₂CHCH₂ .009 F I CH₂CHCH₂ .010 H CH₃ CH₂CHCH₂ .011 Cl CH₃ CH₂CHCH₂ .012 F CH₃ CH₂CHCH₂ .013 H OH CH₂CHCH₂ .014 Cl OH CH₂CHCH₂ .015 F OH CH₂CHCH₂ .016 H OCF₃ CH₂CHCH₂ .017 Cl OCF₃ CH₂CHCH₂ .018 F OCF₃ CH₂CHCH₂ .019 H CHO CH₂CHCH₂ .020 Cl CHO CH₂CHCH₂ .021 F CHO CH₂CHCH₂ .022 H CHF₂ CH₂CHCH₂ .023 Cl CHF₂ CH₂CHCH₂ .024 F CHF₂ CH₂CHCH₂ .025 H COOH CH₂CHCH₂ .026 Cl COOH CH₂CHCH₂ .027 F COOH CH₂CHCH₂ .028 H COOCH₂CH₃ CH₂CHCH₂ .029 Cl COOCH₂CH₃ CH₂CHCH₂ .030 F COOCH₂CH₃ CH₂CHCH₂ .031 H CN CH₂CHCH₂ .032 Cl CN CH₂CHCH₂ .033 F CN CH₂CHCH₂ .034 H Cl CH₂C₆H₅ .035 Cl Cl CH₂C₆H₅ .036 F Cl CH₂C₆H₅ .037 H Br CH₂C₆H₅ .038 Cl Br CH₂C₆H₅ .039 F Br CH₂C₆H₅ .040 H I CH₂C₆H₅ .041 Cl I CH₂C₆H₅ .042 F I CH₂C₆H₅ .043 H CH₃ CH₂C₆H₅ .044 Cl CH₃ CH₂C₆H₅ .045 F CH₃ CH₂C₆H₅ .046 H OH CH₂C₆H₅ .047 Cl OH CH₂C₆H₅ .048 F OH CH₂C₆H₅ .049 H OCF₃ CH₂C₆H₅ .050 Cl OCF₃ CH₂C₆H₅ .051 F OCF₃ CH₂C₆H₅ .052 H CHO CH₂C₆H₅ .053 Cl CHO CH₂C₆H₅ .054 F CHO CH₂C₆H₅ .055 H CHF₂ CH₂C₆H₅ .056 Cl CHF₂ CH₂C₆H₅ .057 F CHF₂ CH₂C₆H₅ .058 H COOH CH₂C₆H₅ .059 Cl COOH CH₂C₆H₅ .060 F COOH CH₂C₆H₅ .061 H COOCH₂CH₃ CH₂C₆H₅ .062 Cl COOCH₂CH₃ CH₂C₆H₅ .063 F COOCH₂CH₃ CH₂C₆H₅ .064 H CN CH₂C₆H₅ .065 Cl CN CH₂C₆H₅ .066 F CN CH₂C₆H₅ .067 H Cl CH₂CCH .068 Cl Cl CH₂CCH .069 F Cl CH₂CCH .070 H Br CH₂CCH .071 Cl Br CH₂CCH .072 F Br CH₂CCH .073 H I CH₂CCH .074 Cl I CH₂CCH .075 F I CH₂CCH .076 H CH₃ CH₂CCH .077 Cl CH₃ CH₂CCH .078 F CH₃ CH₂CCH .079 H OH CH₂CCH .080 Cl OH CH₂CCH .081 F OH CH₂CCH .082 H OCF₃ CH₂CCH .083 Cl OCF₃ CH₂CCH .084 F OCF₃ CH₂CCH .085 H CHO CH₂CCH .086 Cl CHO CH₂CCH .087 F CHO CH₂CCH .088 H CHF₂ CH₂CCH .089 Cl CHF₂ CH₂CCH .090 F CHF₂ CH₂CCH .091 H COOH CH₂CCH .092 Cl COOH CH₂CCH .093 F COOH CH₂CCH .094 H COOCH₂CH₃ CH₂CCH .095 Cl COOCH₂CH₃ CH₂CCH .096 F COOCH₂CH₃ CH₂CCH .097 H CN CH₂CCH .098 Cl CN CH₂CCH .099 F CN CH₂CCH .100 H Cl CH₂COOH .101 Cl Cl CH₂COOH .102 F Cl CH₂COOH .103 H Br CH₂COOH .104 Cl Br CH₂COOH .105 F Br CH₂COOH .106 H I CH₂COOH .107 Cl I CH₂COOH .108 F I CH₂COOH .109 H CH₃ CH₂COOH .110 Cl CH₃ CH₂COOH .111 F CH₃ CH₂COOH .112 H OH CH₂COOH .113 Cl OH CH₂COOH .114 F OH CH₂COOH .115 H OCF₃ CH₂COOH .116 Cl OCF₃ CH₂COOH .117 F OCF₃ CH₂COOH .118 H CHO CH₂COOH .119 Cl CHO CH₂COOH .120 F CHO CH₂COOH .121 H CHF₂ CH₂COOH .122 Cl CHF₂ CH₂COOH .123 F CHF₂ CH₂COOH .124 H COOH CH₂COOH .125 Cl COOH CH₂COOH .126 F COOH CH₂COOH .127 H COOCH₂CH₃ CH₂COOH .128 Cl COOCH₂CH₃ CH₂COOH .129 F COOCH₂CH₃ CH₂COOH .130 H CN CH₂COOH .131 Cl CN CH₂COOH .132 F CN CH₂COOH .133 H Cl CH₂COOCH₃ .134 Cl Cl CH₂COOCH₃ .135 F Cl CH₂COOCH₃ .136 H Br CH₂COOCH₃ .137 Cl Br CH₂COOCH₃ .138 F Br CH₂COOCH₃ .139 H I CH₂COOCH₃ .140 Cl I CH₂COOCH₃ .141 F I CH₂COOCH₃ .142 H CH₃ CH₂COOCH₃ .143 Cl CH₃ CH₂COOCH₃ .144 F CH₃ CH₂COOCH₃ .145 H OH CH₂COOCH₃ .146 Cl OH CH₂COOCH₃ .147 F OH CH₂COOCH₃ .148 H OCF₃ CH₂COOCH₃ .149 Cl OCF₃ CH₂COOCH₃ .150 F OCF₃ CH₂COOCH₃ .151 H CHO CH₂COOCH₃ .152 Cl CHO CH₂COOCH₃ .153 F CHO CH₂COOCH₃ .154 H CHF₂ CH₂COOCH₃ .155 Cl CHF₂ CH₂COOCH₃ .156 F CHF₂ CH₂COOCH₃ .157 H COOH CH₂COOCH₃ .158 Cl COOH CH₂COOCH₃ .159 F COOH CH₂COOCH₃ .160 H COOCH₂CH₃ CH₂COOCH₃ .161 Cl COOCH₂CH₃ CH₂COOCH₃ .162 F COOCH₂CH₃ CH₂COOCH₃ .163 H CN CH₂COOCH₃ .164 Cl CN CH₂COOCH₃ .165 F CN CH₂COOCH₃ .166 H Cl OH .167 Cl Cl OH .168 F Cl OH .169 H Br OH .170 Cl Br OH .171 Br Br OH .172 H I OH .173 Cl I OH .174 F I OH .175 H CH₃ OH .176 Cl CH₃ OH .177 F CH₃ OH .178 H OH OH .179 Cl OH OH .180 F OH OH .181 H OCF₃ OH .182 Cl OCF₃ OH .183 F OCF₃ OH .184 H CHO OH .185 Cl CHO OH .186 F CHO OH .187 H CHF₂ OH .188 Cl CHF₂ OH .189 F CHF₂ OH .190 H COOH OH .191 Cl COOH OH .192 F COOH OH .193 H COOCH₂CH₃ OH .194 Cl COOCH₂CH₃ OH .195 F COOCH₂CH₃ OH .196 H CN OH .197 Cl CN OH .198 F CN OH .199 H Cl OCH₂CHCH₂ .200 Cl Cl OCH₂CHCH₂ .201 F Cl OCH₂CHCH₂ .202 H Br OCH₂CHCH₂ .203 Cl Br OCH₂CHCH₂ .204 F Br OCH₂CHCH₂ .205 H I OCH₂CHCH₂ .206 Cl I OCH₂CHCH₂ .207 F I OCH₂CHCH₂ .208 H CH₃ OCH₂CHCH₂ .209 Cl CH₃ OCH₂CHCH₂ .210 F CH₃ OCH₂CHCH₂ .211 H OH OCH₂CHCH₂ .212 Cl OH OCH₂CHCH₂ .213 F OH OCH₂CHCH₂ .214 H OCF₃ OCH₂CHCH₂ .215 Cl OCF₃ OCH₂CHCH₂ .216 F OCF₃ OCH₂CHCH₂ .217 H CHO OCH₂CHCH₂ .218 Cl CHO OCH₂CHCH₂ .219 F CHO OCH₂CHCH₂ .220 H CHF₂ OCH₂CHCH₂ .221 Cl CHF₂ OCH₂CHCH₂ .222 F CHF₂ OCH₂CHCH₂ .223 H COOH OCH₂CHCH₂ .224 Cl COOH OCH₂CHCH₂ .225 F COOH OCH₂CHCH₂ .226 H COOCH₂CH₃ OCH₂CHCH₂ .227 Cl COOCH₂CH₃ OCH₂CHCH₂ .228 F COOCH₂CH₃ OCH₂CHCH₂ .229 H CN OCH₂CHCH₂ .230 Cl CN OCH₂CHCH₂ .231 F CN OCH₂CHCH₂ .232 H Cl OCH₂C₆H₅ .233 Cl Cl OCH₂C₆H₅ .234 F Cl OCH₂C₆H₅ .235 H Br OCH₂C₆H₅ .236 Cl Br OCH₂C₆H₅ .237 F Br OCH₂C₆H₅ .238 H I OCH₂C₆H₅ .239 Cl I OCH₂C₆H₅ .240 F I OCH₂C₆H₅ .241 H CH₃ OCH₂C₆H₅ .242 Cl CH₃ OCH₂C₆H₅ .243 F CH₃ OCH₂C₆H₅ .244 H OH OCH₂C₆H₅ .245 Cl OH OCH₂C₆H₅ .246 F OH OCH₂C₆H₅ .247 H OCF₃ OCH₂C₆H₅ .248 Cl OCF₃ OCH₂C₆H₅ .249 F OCF₃ OCH₂C₆H₅ .250 H CHO OCH₂C₆H₅ .251 Cl CHO OCH₂C₆H₅ .252 F CHO OCH₂C₆H₅ .253 H CHF₂ OCH₂C₆H₅ .254 Cl CHF₂ OCH₂C₆H₅ .255 F CHF₂ OCH₂C₆H₅ .256 H COOH OCH₂C₆H₅ .257 Cl COOH OCH₂C₆H₅ .258 F COOH OCH₂C₆H₅ .259 H COOCH₂CH₃ OCH₂C₆H₅ .260 Cl COOCH₂CH₃ OCH₂C₆H₅ .261 F COOCH₂CH₃ OCH₂C₆H₅ .262 H CN OCH₂C₆H₅ .263 Cl CN OCH₂C₆H₅ .264 F CN OCH₂C₆H₅ .265 H Cl OCH₂COOH .266 Cl Cl OCH₂COOH .267 F Cl OCH₂COOH .268 H Br OCH₂COOH .269 Cl Br OCH₂COOH .270 F Br OCH₂COOH .271 H I OCH₂COOH .272 Cl I OCH₂COOH .273 F I OCH₂COOH .274 H CH₃ OCH₂COOH .275 Cl CH₃ OCH₂COOH .276 F CH₃ OCH₂COOH .277 H OH OCH₂COOH .278 Cl OH OCH₂COOH .279 F OH OCH₂COOH .280 H OCF₃ OCH₂COOH .281 Cl OCF₃ OCH₂COOH .282 F OCF₃ OCH₂COOH .283 H CHO OCH₂COOH .284 Cl CHO OCH₂COOH .285 F CHO OCH₂COOH .286 H CHF₂ OCH₂COOH .287 Cl CHF₂ OCH₂COOH .288 F CHF₂ OCH₂COOH .289 H COOH OCH₂COOH .290 Cl COOH OCH₂COOH .291 F COOH OCH₂COOH .292 H COOCH₂CH₃ OCH₂COOH .293 Cl COOCH₂CH₃ OCH₂COOH .294 F COOCH₂CH₃ OCH₂COOH .295 H CN OCH₂COOH .296 Cl CN OCH₂COOH .297 F CN OCH₂COOH .298 H Cl OCH₂COOCH₃ .299 Cl Cl OCH₂COOCH₃ .300 F Cl OCH₂COOCH₃ .301 H Br OCH₂COOCH₃ .302 Cl Br OCH₂COOCH₃ .303 F Br OCH₂COOCH₃ .304 H I OCH₂COOCH₃ .305 Cl I OCH₂COOCH₃ .306 F I OCH₂COOCH₃ .307 H CH₃ OCH₂COOCH₃ .308 Cl CH₃ OCH₂COOCH₃ .309 F CH₃ OCH₂COOCH₃ .310 H OH OCH₂COOCH₃ .311 Cl OH OCH₂COOCH₃ .312 F OH OCH₂COOCH₃ .313 H OCF₃ OCH₂COOCH₃ .314 Cl OCF₃ OCH₂COOCH₃ .315 F OCF₃ OCH₂COOCH₃ .316 H CHO OCH₂COOCH₃ .317 Cl CHO OCH₂COOCH₃ .318 F CHO OCH₂COOCH₃ .319 H CHF₂ OCH₂COOCH₃ .320 Cl CHF₂ OCH₂COOCH₃ .321 F CHF₂ OCH₂COOCH₃ .322 H COOH OCH₂COOCH₃ .323 Cl COOH OCH₂COOCH₃ .324 F COOH OCH₂COOCH₃ .325 H COOCH₂CH₃ OCH₂COOCH₃ .326 Cl COOCH₂CH₃ OCH₂COOCH₃ .327 F COOCH₂CH₃ OCH₂COOCH₃ .328 H CN OCH₂COOCH₃ .329 Cl CN OCH₂COOCH₃ .330 F CN OCH₂COOCH₃ .331 H C CH₂CHO .332 Cl Cl CH₂CHO .333 F Cl CH₂CHO .334 H Br CH₂CHO .335 Cl Br CH₂CHO .336 F Br CH₂CHO .337 H I CH₂CHO .338 Cl I CH₂CHO .339 F I CH₂CHO .340 H CH₃ CH₂CHO .341 Cl CH₃ CH₂CHO .342 F CH₃ CH₂CHO .343 H OH CH₂CHO .344 Cl OH CH₂CHO .345 F OH CH₂CHO .346 H OCF₃ CH₂CHO .347 Cl OCF₃ CH₂CHO .348 F OCF₃ CH₂CHO .349 H CHO CH₂CHO .350 Cl CHO CH₂CHO .351 F CHO CH₂CHO .352 H CHF₂ CH₂CHO .353 Cl CHF₂ CH₂CHO .354 F CHF₂ CH₂CHO .355 H COOH CH₂CHO .356 Cl COOH CH₂CHO .357 F COOH CH₂CHO .358 H COOCH₂CH₃ CH₂CHO .359 Cl COOCH₂CH₃ CH₂CHO .360 F COOCH₂CH₃ CH₂CHO .361 H CN CH₂CHO .362 Cl CN CH₂CHO .363 F CN CH₂CHO .364 H Cl OCH₂CHO .365 Cl Cl OCH₂CHO .366 F Cl OCH₂CHO .367 H Br OCH₂CHO .368 Cl Br OCH₂CHO .369 F Br OCH₂CHO .370 H I OCH₂CHO .371 Cl I OCH₂CHO .372 F I OCH₂CHO .373 H CH₃ OCH₂CHO .374 Cl CH₃ OCH₂CHO .375 F CH₃ OCH₂CHO .376 H OH OCH₂CHO .377 Cl OH OCH₂CHO .378 F OH OCH₂CHO .379 H OCF₃ OCH₂CHO .380 Cl OCF₃ OCH₂CHO .381 F OCF₃ OCH₂CHO .382 H CHO OCH₂CHO .383 Cl CHO OCH₂CHO .384 F CHO OCH₂CHO .385 H CHF₂ OCH₂CHO .386 Cl CHF₂ OCH₂CHO .387 F CHF₂ OCH₂CHO .388 H COOH OCH₂CHO .389 Cl COOH OCH₂CHO .390 F COOH OCH₂CHO .391 H COOCH₂CH₃ OCH₂CHO .392 Cl COOCH₂CH₃ OCH₂CHO .393 F COOCH₂CH₃ OCH₂CHO .394 H CN OCH₂CHO .395 Cl CN OCH₂CHO .396 F CN OCH₂CHO .397 H Cl OCH₃ .398 Cl Cl OCH₃ .399 F Cl OCH₃ .400 H Br OCH₃ .401 Cl Br OCH₃ .402 F Br OCH₃ .403 H I OCH₃ .404 Cl I OCH₃ .405 F I OCH₃ .406 H CH₃ OCH₃ .407 Cl CH₃ OCH₃ .408 F CH₃ OCH₃ .409 H OH OCH₃ .410 Cl OH OCH₃ .411 F OH OCH₃ .412 H OCF₃ OCH₃ .413 Cl OCF₃ OCH₃ .414 F OCF₃ OCH₃ .415 H CHO OCH₃ .416 Cl CHO OCH₃ .417 F CHO OCH₃ .418 H CHF₂ OCH₃ .419 Cl CHF₂ OCH₃ .420 F CHF₂ OCH₃ .421 H COOH OCH₃ .422 Cl COOH OCH₃ .423 F COOH OCH₃ .424 H COOCH₂CH₃ OCH₃ .425 Cl COOCH₂CH₃ OCH₃ .426 F COOCH₂CH₃ OCH₃ .427 H CN OCH₃ .428 Cl CN OCH₃ .429 F CN OCH₃ .430 H Cl CH₂OCH₃ .431 Cl Cl CH₂OCH₃ .432 F Cl CH₂OCH₃ .433 H Br CH₂OCH₃ .434 Cl Br CH₂OCH₃ .435 F Br CH₂OCH₃ .436 H I CH₂OCH₃ .437 Cl I CH₂OCH₃ .438 F I CH₂OCH₃ .439 H CH₃ CH₂OCH₃ .440 Cl CH₃ CH₂OCH₃ .441 F CH₃ CH₂OCH₃ .442 H OH CH₂OCH₃ .443 Cl OH CH₂CCH₃ .444 F OH CH₂OCH₃ .445 H OCF₃ CH₂OCH₃ .446 Cl OCF₃ CH₂OCH₃ .447 F OCF₃ CH₂OCH₃ .448 H CHO CH₂OCH₃ .449 Cl CHO CH₂OCH₃ .450 F CHO CH₂OCH₃ .451 H CHF₂ CH₂OCH₃ .452 Cl CHF₂ CH₂OCH₃ .453 F CHF₂ CH₂OCH₃ .454 H COOH CH₂OCH₃ .455 Cl COOH CH₂OCH₃ .456 F COOH CH₂OCH₃ .457 H COOCH₂CH₃ CH₂OCH₃ .458 Cl COOCH₂CH₃ CH₂OCH₃ .459 F COOCH₂CH₃ CH₂OCH₃ .460 H CN CH₂OCH₃ .461 Cl CN CH₂OCH₃ .462 F CN CH₂OCH₃ .463 H Cl CH₂SCH₃ .464 Cl Cl CH₂SCH₃ .465 F Cl CH₂SCH₃ .466 H Br CH₂SCH₃ .467 Cl Br CH₂SCH₃ .468 F Br CH₂SCH₃ .469 H I CH₂SCH₃ .470 Cl I CH₂SCH₃ .471 F I CH₂SCH₃ .472 H CH₃ CH₂SCH₃ .473 Cl CH₃ CH₂SCH₃ .474 F CH₃ CH₂SCH₃ .475 H OH CH₂SCH₃ .476 Cl OH CH₂SCH₃ .477 F OH CH₂SCH₃ .478 H OCF₃ CH₂SCH₃ .479 Cl OCF₃ CH₂SCH₃ .480 F OCF₃ CH₂SCH₃ .481 H CHO CH₂SCH₃ .482 Cl CHO CH₂SCH₃ .483 F CHO CH₂SCH₃ .484 H CHF₂ CH₂SCH₃ .485 Cl CHF₂ CH₂SCH₃ .486 F CHF₂ CH₂SCH₃ .487 H COOH CH₂SCH₃ .488 Cl COOH CH₂SCH₃ .489 F COOH CH₂SCH₃ .490 H COOCH₂CH₃ CH₂SCH₃ .491 Cl COOCH₂CH₃ CH₂SCH₃ .492 F COOCH₂CH₃ CH₂SCH₃ .493 H CN CH₂SCH₃ .494 Cl CN CH₂SCH₃ .495 F CN CH₂SCH₃ .496 H Cl OCH₂OCH₃ .497 Cl Cl OCH₂OCH₃ .498 F Cl OCH₂OCH₃ .499 H Br OCH₂OCH₃ .500 Cl Br OCH₂OCH₃ .501 F Br OCH₂OCH₃ .502 H I OCH₂OCH₃ .503 Cl 1 OCH₂OCH₃ .504 F I OCH₂OCH₃ .505 H CH₃ OCH₂OCH₃ .506 Cl CH₃ OCH₂OCH₃ .507 F CH₃ OCH₂OCH₃ .508 H OH OCH₂OCH₃ .509 Cl OH OCH₂OCH₃ .510 F OH OCH₂OCH₃ .511 H OCF₃ OCH₂OCH₃ .512 Cl OCF₃ OCH₂OCH₃ .513 F OCF₃ OCH₂OCH₃ .514 H CHO OCH₂OCH₃ .515 Cl CHO OCH₂OCH₃ .516 F CHO OCH₂OCH₃ .517 H CHF₂ OCH₂OCH₃ .518 Cl CHF₂ OCH₂OCH₃ .519 F CHF₂ OCH₂OCH₃ .520 H COOH OCH₂OCH₃ .521 Cl COOH OCH₂OCH₃ .522 F COOH OCH₂OCH₃ .523 H COOCH₂CH₃ OCH₂OCH₃ .524 Cl COOCH₂CH₃ OCH₂OCH₃ .525 F COOCH₂CH₃ OCH₂OCH₃ .526 H CN OCH₂OCH₃ .527 Cl CN OCH₂OCH₃ .528 F CN OCH₂OCH₃ .529 H Cl OCH₂SCH₃ .530 Cl Cl OCH₂SCH₃ .531 F Cl OCH₂SCH₃ .532 H Br OCH₂SCH₃ .533 Cl Br OCH₂SCH₃ .534 F Br OCH₂SCH₃ .535 H I OCH₂SCH₃ .536 Cl I OCH₂SCH₃ .537 F I OCH₂SCH₃ .538 H CH₃ OCH₂SCH₃ .539 Cl CH₃ OCH₂SCH₃ .540 F CH₃ OCH₂SCH₃ .541 H OH OCH₂SCH₃ .542 Cl OH OCH₂SCH₃ .543 F OH OCH₂SCH₃ .544 H OCF₃ OCH₂SCH₃ .545 Cl OCF₃ OCH₂SCH₃ .546 F OCF₃ OCH₂SCH₃ .547 H CHO OCH₂SCH₃ .548 Cl CHO OCH₂SCH₃ .549 F CHO OCH₂SCH₃ .550 H CHF₂ OCH₂SCH₃ .551 Cl CHF₂ OCH₂SCH₃ .552 F CHF₂ OCH₂SCH₃ .553 H COOH OCH₂SCH₃ .554 Cl COOH OCH₂SCH₃ .555 F COOH OCH₂SCH₃ .556 H COOCH₂CH₃ OCH₂SCH₃ .557 Cl COOCH₂CH₃ OCH₂SCH₃ .558 F COOCH₂CH₃ OCH₂SCH₃ .559 H CN OCH₂SCH₃ .560 Cl CN OCH₂SCH₃ .561 F CN OCH₂SCH₃ .562 H Cl OCH₂CH₂CN .563 Cl Cl OCH₂CH₂CN .564 F Cl OCH₂CH₂CN .565 H Br OCH₂CH₂CN .566 Cl Br OCH₂CH₂CN .567 F Br OCH₂CH₂CN .568 H I OCH₂CH₂CN .569 Cl I OCH₂CH₂CN .570 F I OCH₂CH₂CN .571 H CH₃ OCH₂CH₂CN .572 Cl CH₃ OCH₂CH₂CN .573 F CH₃ OCH₂CH₂CN .574 H OH OCH₂CH₂CN .575 Cl OH OCH₂CH₂CN .576 F OH OCH₂CH₂CN .577 H OCF₃ OCH₂CH₂CN .578 Cl OCF₃ OCH₂CH₂CN .579 F OCF₃ OCH₂CH₂CN .580 H CHO OCH₂CH₂CN .581 Cl CHO OCH₂CH₂CN .582 F CHO OCH₂CH₂CN .583 H CHF₂ OCH₂CH₂CN .584 Cl CHF₂ OCH₂CH₂CN .585 F CHF₂ OCH₂CH₂CN .586 H COOH OCH₂CH₂CN .587 Cl COOH OCH₂CH₂CN .588 F COOH OCH₂CH₂CN .589 H COOCH₂CH₃ OCH₂CH₂CN .590 Cl COOCH₂CH₃ OCH₂CH₂CN .591 F COOCH₂CH₃ OCH₂CH₂CN .592 H CN OCH₂CH₂CN .593 Cl CN OCH₂CH₂CN .594 F CN OCH₂CH₂CN .595 H Cl CH₂CH₂CN .596 Cl Cl CH₂CH₂CN .597 F Cl CH₂CH₂CN .598 H Br CH₂CH₂CN .599 Cl Br CH₂CH₂CN .600 F Br CH₂CH₂CN .601 H I CH₂CH₂CN .602 Cl I CH₂CH₂CN .603 F I CH₂CH₂CN .604 H CH₃ CH₂CH₂CN .605 Cl CH₃ CH₂CH₂CN .606 F CH₃ CH₂CH₂CN .607 H OH CH₂CH₂CN .608 Cl OH CH₂CH₂CN .609 F OH CH₂CH₂CN .610 H OCF₃ CH₂CH₂CN .611 Cl OCF₃ CH₂CH₂CN .612 F OCF₃ CH₂CH₂CN .613 H CHO CH₂CH₂CN .614 Cl CHO CH₂CH₂CN .615 F CHO CH₂CH₂CN .616 H CHF₂ CH₂CH₂CN .617 Cl CHF₂ CH₂CH₂CN .618 F CHF₂ CH₂CH₂CN .619 H COOH CH₂CH₂CN .620 Cl COOH CH₂CH₂CN .621 F COOH CH₂CH₂CN .622 H COOCH₂CH₃ CH₂CH₂CN .623 Cl COOCH₂CH₃ CH₂CH₂CN .624 F COOCH₂CH₃ CH₂CH₂CN .625 H CN CH₂CH₂CN .626 Cl CN CH₂CH₂CN .627 F CN CH₂CH₂CN

TABLE E Prepared compounds from the above Tables with physicochemical data. The numbers in front of the point designates the number of the Table e.g. 1.150 signifies in Table 1 the compound No. 150 of Table A and 72.133 signifies in Table 72 the compound No. 133 of Table B. Compd. No. Physicochemical data 1.001 m.p. 137-139° C. 1.002 m.p. 142-146° C. 1.003 m.p. 122-124° C. 1.004 amorphous (Example P45) 1.007 solid 1.010 resin 1.015 m.p. 76-78° C. 1.031 m.p. 88-90° C. 1.045 m.p. 85-86° C. 1.080 resin (Example P44) 1.100 m.p. 104-106° C. 1.105 m.p. 105-107° C. 1.106 resin 1.111 m.p. 93-94° C. 1.126 m.p. 104-106° C. 1.137 m.p. 89-93° C. 1.147 resin. (Example P51) 1.150 m.p. 137-138° C. 1.152 m.p. 167-168° C. 1.153 m.p. 171-172° C. (Example P52) 1.155 m.p. 102-104° C. 1.156 m.p. 113-114° C. 1.161 m.p. 143-145° C. (Example P53) 1.162 m.p. 180-182° C. 1.168 m.p. 122-124° C. 1.177 solid (Example P47) 1.181 amorphous 1.182 m.p. 98-100° C. 1.190 oil 1.195 m.p. 83-85° C. (Example P46) 1.205 resin 1.216 m.p. 80-86° C. 1.234 amorphous (Example P49) 1.244 m.p. 146-148° C. (Example P50) 1.294 oil (Example P55) 1.302 m.p. 102-104° C. 1.397 resin (Example P32) 1.400 resin (Example P33) 1.422 m.p. 100-101° C. 1.494 m.p. 135-138° C. (Example P54) 7.100 m.p. 111-113° C. 9.002 resin 9.100 m.p. 110-112° C. 10.100 m.p. 126-127° C. 22.002 m.p. 131-133° C. 22.100 m.p. 190-191° C. (Example P43) 28.100 m.p. 189-192° C. (Example P42) 72.083 m.p. 152-153° C. (Example P60) 72.113 m.p. 250° C. (decomposition) (Example P59) 72.133 m.p. 140-143° C. (Example P58)

Examples of specific formulations of the compounds of formula I, such as emulsifiable concentrates, solutions, wettable powders, coated, granules, extruder granules, dusts and suspension concentrates, are described in WO 97/34485, pages 9 to 13.

BIOLOGICAL EXAMPLES Example B1:

Herbicidal Action Prior to Emergence of the Plants (Pre-Emergence Action)

Monocotyledonous and dicotyledonous test plants are sown in standard soil in plastics pots. Immediately after sowing, the test compounds, each in the form of an aqueous suspension or emulsion prepared from a 25% emulsifiable concentrate (Example F1, c) in WO 97/34485, pages 9 and 10), are applied by spraying at a rate of application of 2000. g of active ingredient/ha (500 liters water/ha). The test plants are then grown in a greenhouse under optimum conditions. After 3 weeks' test duration, the test is evaluated in accordance with a scale of nine ratings (1=total damage, 9=no action). Ratings of from 1 to 4 (especially from 1 to 3) indicate good to very good herbicidal action.

Test plants: Avena, Setaria, Sinapis, Stellaria

The compounds according to the invention exhibit a good herbicidal action.

Examples of the good herbicidal activity of the compounds of formula I are given in Table B1.

TABLE B1 Pre-emergence action: Test plant Concentration Compd. No. Avena Setaria Sinapis Stellaria [g a.i./ha] 1.001 1 1 1 1 2000 1.002 1 1 1 1 2000 1.003 1 1 1 1 2000 1.004 1 1 1 1 2000 1.010 1 1 1 1 2000 1.080 1 1 1 1 2000 1.100 1 1 1 1 2000 1.105 1 1 1 1 2000 1.106 2 1 1 1 2000 1.111 2 1 1 1 2000 1.126 1 1 1 1 2000 1.147 1 1 1 1 2000 1.150 1 1 1 1 2000 1.152 1 1 1 1 2000 1.153 1 1 1 1 2000 1.156 1 1 1 1 2000 1.168 1 1 1 1 2000 1.181 1 1 1 1 2000 1.190 2 1 1 1 2000 1.195 3 1 1 1 2000 1.205 1 1 1 1 2000 1.302 1 1 1 1 2000 1.400 1 1 1 1 2000 7.100 1 1 1 1 2000 9.002 1 3 1 1 2000 9.100 1 1 1 1 2000 10.100 1 1 1 1 2000 28.100 1 1 1 1 2000

The same results are obtained when compounds of formula I are formulated according to Examples F2 to F8 in WO 97/34485, pages 10 to 12.

Example B2:

Post-Emergence Herbicidal Action

Monocotyledonous and dicotyledonous test plants are grown in a greenhouse in plastics pots containing standard soil and at the 4- to 6-leaf stage are sprayed with an aqueous suspension or emulsion of the test substances of formula I, prepared from a 25% emulsifiable concentrate (Example F1, c) in WO 97/34485, pages 9 and 10), at a rate of application corresponding to 2000 g of active ingredient/ha (500 liters water/ha). The test plants are then grown on in the greenhouse under optimum conditions. After approximately 18 days' test duration, the test is evaluated in accordance with a scale of nine ratings (1=total damage, 9=no action). Ratings of from 1 to 4 (especially from 1 to 3) indicate good to very good herbicidal action.

Test plants: Avena, Setaria, Sinapis, Stellaria

In this test, too, the compounds of formula I exhibit a strong herbicidal action.

Examples of the good herbicidal activity of the compounds of formula I are given in Table B2.

TABLE B2 Post-emergence action: Test plant Concentration Compd. No. Avena Setaria Sinapis Stellaria [g a.i./ha] 1.001 1 1 1 1 2000 1.002 1 1 1 1 2000 1.003 1 1 1 1 2000 1.004 1 2 1 1 2000 1.010 1 1 1 1 2000 1.080 1 1 1 1 2000 1.100 1 1 1 1 2000 1.105 1 2 1 1 2000 1.106 3 3 1 1 2000 1.111 2 1 1 2 2000 1.126 1 1 1 1 2000 1.147 1 1 1 1 2000 1.150 1 1 1 1 2000 1.152 1 1 1 1 2000 1.153 1 1 1 1 2000 1.156 1 1 1 1 2000 1.168 1 1 1 1 2000 1.181 1 1 1 1 2000 1.190 1 1 1 1 2000 1.195 1 1 1 1 2000 1.205 1 1 1 1 2000 1.302 1 1 1 1 2000 1.400 1 2 1 1 2000 7.100 1 1 1 1 2000 9.002 1 3 1 1 2000 9.100 2 2 1 1 2000 10.100 1 2 1 1 2000 28.100 1 1 1 1 2000

The same results are obtained when the compounds of formula I are formulated according to Examples F2 to F8 in WO 97/34485, pages 10 to 12. 

What is claimed is:
 1. A compound of formula I

wherein

R₁ is hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl, cyano-C₁-C₄alkyl, C₃- or C₄-alkenyl, C₃- or C₄-haloalkenyl, C₃- or C₄-alkynyl or C₃-C₆cycloalkyl; R₂ is hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₃-C₆alkenyl, C₃-C₆haloalkenyl, C₃-C₆alkynyl, C₁-C₄alkyl-S(O)₂— or C₁-C₄haloalkyl-S(O)₂—; R₃ is hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, halogen, cyano, NH₂C(S)—, nitro or amino; n, is 0, 1 or 2; R₄ is hydrogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₃-C₆alkenyl, C₃-C₆haloalkenyl, C₃-C₆alkynyl or C₃-C₆cycloalkyl; R₅ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, cyano, nitro, amino, NH₂C(O)—, NH₂C(S)—, C₁-C₄alkylcarbonyl, C₁-C₆alkoxycarbonyl, C₁-C₄haloalkylcarbonyl, C₂-C₄allenylcarbonyl, C₁-C₃alkyl-CH(OH)—, OHC—, HOC(O)—, ClC(O)—, HON═CH—, C₁-C₄alkoxy-N═CH—, C₂-C₄haloalkenylcarbonyl or C₂-C₄alkynylcarbonyl; R₁₁ is hydrogen, fluorine, chlorine, bromine or methyl; R₁₂ is hydrogen, halogen, methyl, halomethyl, nitro, amino, hydroxy, OHC—, HOC(O)—, cyano, C₁-C₄alkoxycarbonyl or halomethoxy; X₁ is O, S, R₂₀N═ or R₂₅ON═; R₁₃ is hydroxy, C₁-C₆alkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy, C₃-C₆-haloalkenyloxy, C₁-C₆alkoxy-C₁-C₆alkyl, C₃-C₆alkenyloxy-C₁-C₆alkyl, C₃-C₆alkynyloxy-C₁-C₆alkyl, C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkyl, B₁—C₁-C₆alkoxy, R₂,(R₂₂)N—, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₂-C₆haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₃-C₆halocycloalkyl, B₁—C₁-C₆alkyl, OHC—, C₁-C₆alkylcarbonyl, C₁-C₆alkylcarbonyloxy, C₁-C₆haloalkylcarbonyl, C₂-C₆alkenylcarbonyl, C₁-C₆alkoxycarbonyl, C₁-C₆alkyl-S(O)₂—, C₁-C₆haloalkyl-S(O)₂—, (C₁-C₆alkyl)₂N—N═CH—,

B₁—CH═N—, (CH₃)₂N—CH═N—, (C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₅haloalkyl)—CH₂—, (hydroxy-C₁-C₅alkyl)—O— or (B₁—C₁-C₅hydroxyalkyl)—O—; B₁ is cyano, OHC—, HOC(O)—, C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl, C₃-C₆alkynyloxycarbonyl, benzyloxycarbonyl, benzyloxycarbonyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, benzylthiocarbonyl, benzylthiocarbonyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄-alkyl or by C₁-C₄haloalkyl, C₁-C₆haloalkoxycarbonyl, C₁-C₆alkylthio-C(O)—, R₂₆(R₂₇)NC(O)—, phenyl, phenyl mono- to tri-substituted by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, C₁-C₆-alkyl-S(O)₂—, C₁-C₆alkyl-S(O)—, C₁-C₆alkylthio, C₃-C₆cycloalkyl, C₁-C₆alkoxy, C₃-C₆alkenylthio or C₃-C₆alkynylthio; R₂₀ is hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₂-C₆haloalkyl, cyano, R₂₃(R₂₄)N—, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl, C₃-C₆alkynyloxycarbonyl, C₂-C₆haloalkoxycarbonyl, OHC—, C₁-C₆alkylcarbonyl, C₁-C₆haloalkylcarbonyl, C₁-C₆alkyl-S(O)₂—, C₁-C₆haloalkyl-S(O)₂—, phenyl, phenyl mono- to tri-substituted by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, phenyl-C₁-C₆alkyl, or phenyl-C₁-C₆alkyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl; R₂₁ and R₂₂ are each independently hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆-haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₁-C₆alkoxy-C₁-C₆alkyl, OHC—, C₁-C₆alkylcarbonyl, C₁-C₆haloalkylcarbonyl, C₁-C₆alkyl-S(O)₂— or C₁-C₆haloalkyl-S(O)₂—; R₂₃ and R₂₄ are each independently as defined for R₂₁; R₂₅ is hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆haloalkyl, C₃-C₆haloalkenyl, C₁-C₆alkoxy, C₁-C₆alkyl, benzyl, C₁-C₆alkyl-S(O)₂— or C₁-C₆haloalkyl-S(O)₂—; R₂₆ and R₂₇ are each independently hydrogen, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆haloalkyl, C₃-C₈haloalkenyl, phenyl, phenyl mono- to tri-substituted by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl, benzyl, or benzyl mono- to tri-substituted at the phenyl ring by halogen, C₁-C₄alkyl or by C₁-C₄haloalkyl; or a pyrazole N-oxide, an agrochemically acceptable salt or a stereoisomer of that compound of formula I.
 2. A compound of formula I according to claim 1 having the formula Ia

wherein

R₁, R₂, R₃, R₄, R₅, R₁₁, R₁₂, R₁₃, X₁ and n₁ are as defined in claim
 1. 3. A process for the preparation of a compound of formula I according to claim 1

wherein R₁₁, R₁₂ and W are as defined in claim 1; X₁ is O or S; R₁₃ is C₁-C₆alkoxy-C₁-C₆-alkyl, C₁-C₆alkoxy-C₁-C₆alkoxy-C₁C₆alkyl, C₁-C₆alkyl, C₃-C₆alkenyl, C₃-C₆alkynyl, C₂-C₆-haloalkyl, C₃-C₆haloalkenyl, C₃-C₆cycloalkyl, C₃-C₆halocycloalkyl, B₁—C₁-C₆alkyl,

(C₁-C₅hydroxyalkyl)—CH₂—, (B₁—C₁-C₆hydroxyalkyl)—CH₂— or (B₁—C₁-C₆haloalkyl)—CH₂—; and B₁ is as defined in claim 1, which comprises oxidising a compound of formula III

in a suitable solvent to form a compound of formula V

and subsequently rearranging that compound in an inert solvent in the presence of an anhydride or in the presence of antimony pentachloride to yield, after aqueous working up, a compound of formula II

the radicals R₁₁, R₁₂ and W in the compounds of formulae II, III and V being as defined above, and then alkylating that compound in the presence of an inert solvent and a base with a compound of formula VI R₁₃—L  (VI), wherein R₁₃ is as defined above and L is a leaving group, to form the compounds of formulae I and IV

wherein R₁₁, R₁₂, R₁₃ and W are as defined above and X₁ is O, and subsequently, where appropriate after separating off the compound of formula I, functionalising the pyridone group thereof according to the definition of X₁ and R₁₃.
 4. A herbicidal and plant-growth-inhibiting composition having a herbicidally effective content of a compound of formula I according to claim 1 and comprising an inert carrier.
 5. A composition according to claim 6 comprising from 0.1% to 95% of a compound of formula I.
 6. A method of controlling undesired plant growth, which comprises applying a compound of formula I, or a composition comprising that compound, in a herbicidally effective amount to the crops of useful plants or to the locus thereof. 